WO2025166413A1

WO2025166413A1 - Compositions and methods for delivering glp-1 agonists (metabolix)

Info

Publication number: WO2025166413A1
Application number: PCT/AU2025/050085
Authority: WO
Inventors: Chin Beng Stephen Lim; Iain Bruce Cook; Yip Hang Eddy Lee; Janakan KRISHNARAJAH
Original assignee: Ix Biopharma Ltd; IX Biopharma Ltd
Current assignee: Ix Biopharma Ltd; IX Biopharma Ltd
Priority date: 2024-02-05
Filing date: 2025-02-05
Publication date: 2025-08-14
Anticipated expiration: 2026-08-05

Abstract

A composition comprising a glucagon-like peptide 1 (GLP-1) agonist for sublingual or buccal administration, wherein the composition comprises one or more agents selected from the group consisting of; sodium glycodeoxycholate; sodium deoxycholate; carboxymethyl cellulose; sodium alginate; SNAC (salcaprozate sodium); a non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate); and soy lecithin.

Description

Compositions and methods for delivering GLP-1 agonists (MetaboliX) Field of the Invention [0001] The present invention relates to compositions comprising a biological active material. The present invention also relates to pharmaceutical compositions, dosage forms and methods for weight management. Background [0002] The following discussion of the background art is intended to facilitate an understanding of the present invention only. The discussion is not an acknowledgement or admission that any of the material referred to is or was part of the common general knowledge as at the priority date of the application. [0003] Semaglutide, Liraglutide and Dapagliflozin [0004] Semaglutide, liraglutide and dapagliflozin are drugs with long term weight loss effect. Both drugs cause more than 7.5% weight loss when taken separately and maintain the weight loss for 24 months and beyond. By combining both drugs into a single unit-dose it will have a synergistic weight loss effect of more than 15% weight loss capability. The doubling effect was due to their different pharmacology action. Dapagliflozin is a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist whereas semaglutide and liraglutide are glucagon-like peptide 1 (GLP-1) agonists. [0005] SGLT2 inhibits protein in the kidneys which is responsible for reabsorbing glucose back into the bloodstream. By blocking this protein, SGLT-2 inhibitors prevent glucose from being reabsorbed and instead promote its excretion in urine. This leads to a reduction in blood glucose levels and glucose calories. [0006] GLP-1 agonist works by mimicking the effects of GLP-1, a hormone that is naturally produced in the body, mostly in the intestine. GLP-1 receptor agonists induce weight loss via the gastrointestinal tract-brain axis, with the primary action of increase in satiety. Also, GLP-1 decreases the secretion of acid in the stomach resulting in a delay of gastric emptying from the stomach, prolonging the sensation of fullness and a loss in appetite. [0007] Semaglutide is designed to mimic the function of natural GLP-1 in the body. Natural or native GLP-1 has a very short half-life of around 1 to 2 min, is rapidly degraded by the enzyme dipeptidylpeptidase-4 (DPP-4), whereas the GLP-1 analogue, semaglutide, is resistant to DPP-4 degradation, increasing and prolonging its duration of action (half-life of 7 days) and reducing the drug administration frequency to once a week dosing. [0008] GLP-1 (a hormone) is primarily produced in the intestine in the L-cells. The L- cells are enteroendocrine cells are open-type epithelial cells in contact directly with nutrients in the intestinal lumen. GLP-1 an incretin hormone, stimulates insulin secretion and inhibits glucagon secretion, playing an important role in regulating glucose metabolism and importantly appetite control (satiety via gut-brain axis). [0009] Semaglutide acts on GLP-1 receptors in the intestines and other organs to stimulate insulin secretion, suppress glucagon release, slow down gastric emptying, reduce appetite, and regulate glucose homeostasis/metabolism, helping to improve glycaemic control, promote weight loss, and manage obesity. [0010] Currently, semaglutide is available as a subcutaneous injection preparation approved for treatment of type 2 diabetes mellitus and obesity plus one oral tablet preparation approved for the treatment of type 2 diabetes mellitus. Semaglutide is less suitable for oral administration due to its very low oral bioavailability (less than 0.1%). The approved oral tablet semaglutide formulation has an oral bioavailability of 0.4 to 1% via stomach absorption. Semaglutide is also easily damaged by the stomach’s gastric acid, digestive enzymes and intestinal mucosa barrier to absorption by passive diffusion against macromolecules penetration leading to poor absorption and low bioavailability. [0011] There is a need in the art for improved compositions and methods for weight loss and weight management. It is an objective of the invention to overcome one or more problems foreshadowed by the prior art. Summary of the Invention [0012] In a first aspect, the invention broadly resides in a composition wherein said composition comprises at least one biologically active material selected from the group consisting of: a glucagon-like peptide 1 (GLP-1) agonist; and a sodium glucose co- transporter-2 (SGLT-2) receptor antagonist. [0013] In a preferred embodiment, the glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of semaglutide; liraglutide; dulaglutide; exenatide; lixisenatide; and any combination thereof, and a pharmaceutically acceptable salt, analog, homolog or derivative thereof. [0014] Preferably, the sodium glucose co-transporter-2 (SGLT-2) receptor antagonist is selected from the group consisting of dapagliflozin; empagliflozin; ertugliflozin; canagliflozin; bexagliflozin; and any combination thereof; and a pharmaceutically acceptable salt, analog, homolog or derivative thereof. [0015] Preferably, the composition comprises two biologically active materials selected from the group consisting of: a glucagon-like peptide 1 (GLP-1) agonist; and a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist. [0016] Preferably, the composition is a solid dosage form. Preferably, the composition is a rapidly disintegrating solid dosage form. Preferably, the composition is a wafer, tablet or capsule. Preferably, the composition is a wafer and is neutral pH protected against the acidic pH and enzymatic degradation in the stomach. [0017] Preferably, the biologically active material is present in the composition at a concentration selected from the group consisting of: 0.01% (w/w); 0.1% (w/w); 1% (w/w); 2% (w/w); 3% (w/w); 4% (w/w); 5% (w/w); 6% (w/w); 7% (w/w); 8% (w/w); 9% (w/w); 10% (w/w); 11% (w/w); 12% (w/w); 13% (w/w); 14% (w/w); 15% (w/w); 16% (w/w); 17% (w/w); 18% (w/w); 19% (w/w); 20% (w/w); 21% (w/w); 22% (w/w); 23% (w/w); 24% (w/w); 25% (w/w); 26% (w/w); 27% (w/w); 28% (w/w); 29% (w/w); 30% (w/w); 31% (w/w); 32% (w/w); 33% (w/w); 34% (w/w); 35% (w/w); 36% (w/w); 37% (w/w); 38% (w/w); 39% (w/w); 40% (w/w); 41% (w/w); 42% (w/w); 43% (w/w); 44% (w/w); 45% (w/w); 46% (w/w); 47% (w/w); 48% (w/w); 49% (w/w); 50% (w/w); 0.2-95% (w/w); and 2-95% (w/w); 33-65% (w/w); 4-55% (w/w); 5-45% (w/w); 6-35% (w/w); 7-25% (w/w); 8-15% (w/w); and within 2 decimal points of each figure. [0018] Preferably, the biologically active material is present in the composition at a quantity selected from the group consisting of: 1ng to 1000mg; 0.01ng to 100mg; 0.01mg; 0.02mg; 0.03mg; 0.04mg; 0.05mg; 0.06mg; 0.07mg; 0.08mg; 0.09mg; 0.10mg; 0.11mg; 0.12mg; 0.13mg; 0.14mg; 0.15mg; 0.16mg; 0.17mg; 0.18mg; 0.19mg; 0.20mg; 0.21mg; 0.22mg; 0.23mg; 0.24mg; 0.25mg; 0.26mg; 0.27mg; 0.28mg; 0.29mg; 0.30mg; 0.31mg; 0.32mg; 0.33mg; 0.34mg; 0.35mg; 0.36mg; 0.37mg; 0.38mg; 0.39mg; 0.40mg; 0.41mg; 0.42mg; 0.43mg; 0.44mg; 0.45mg; 0.46mg; 0.47mg; 0.48mg; 0.49mg; 0.50mg; 0.51mg; 0.52mg; 0.53mg; 0.54mg; 0.55mg; 0.56mg; 0.57mg; 0.58mg; 0.59mg; 0.60mg; 0.61mg; 0.62mg; 0.63mg; 0.64mg; 0.65mg; 0.66mg; 0.67mg; 0.68mg; 0.69mg; 0.70mg; 0.71mg; 0.72mg; 0.73mg; 0.74mg; 0.75mg; 0.76mg; 0.77mg; 0.78mg; 0.79mg; 0.80mg; 0.81mg; 0.82mg; 0.83mg; 0.84mg; 0.85mg; 0.86mg; 0.87mg; 0.88mg; 0.89mg; 0.90mg; 0.91mg; 0.92mg; 0.93mg; 0.94mg; 0.95mg; 0.96mg; 0.97mg; 0.98mg; 0.99mg; 1.00mg; 0.1mg; 0.2mg; 0.3mg; 0.4mg; 0.5mg; 0.6mg; 0.7mg; 0.8mg; 0.9mg; 1.0mg; 1mg; 2mg; 3mg; 4mg; 5mg; 6mg; 7mg; 8mg; 9mg; 10mg; 11mg; 12mg; 13mg; 14mg; 15mg; 16mg; 17mg; 18mg; 19mg; 20mg; 21mg; 22mg; 23mg; 24mg; 25mg; 26mg; 27mg; 28mg; 29mg; 30mg; 31mg; 32mg; 33mg; 34mg; 35mg; 36mg; 37mg; 38mg; 39mg; 40mg; 41mg; 42mg; 43mg; 44mg; 45mg; 46mg; 47mg; 48mg; 49mg; 50mg; 51mg; 52mg; 53mg; 54mg; 55mg; 56mg; 57mg; 58mg; 59mg; 60mg; 61mg; 62mg; 63mg; 64mg; 65mg; 66mg; 67mg; 68mg; 69mg; 70mg; 71mg; 72mg; 73mg; 74mg; 75mg; 76mg; 77mg; 78mg; 79mg; 80mg; 81mg; 82mg; 83mg; 84mg; 85mg; 86mg; 87mg; 88mg; 89mg; 90mg; 91mg; 92mg; 93mg; 94mg; 95mg; 96mg; 97mg; 98mg; 99mg; 100mg; 101mg; 102mg; 103mg; 104mg; 105mg; 106mg; 107mg; 108mg; 109mg; 110mg; 111mg; 112mg; 113mg; 114mg; 115mg; 116mg; 117mg; 118mg; 119mg; 120mg; 121mg; 122mg; 123mg; 124mg; 125mg; 126mg; 127mg; 128mg; 129mg; 130mg; 131mg; 132mg; 133mg; 134mg; 135mg; 136mg; 137mg; 138mg; 139mg; 140mg; 141mg; 142mg; 143mg; 144mg; 145mg; 146mg; 147mg; 148mg; 149mg; 150mg; 151mg; 152mg; 153mg; 154mg; 155mg; 156mg; 157mg; 158mg; 159mg; 160mg; 161mg; 162mg; 163mg; 164mg; 165mg; 166mg; 167mg; 168mg; 169mg; 170mg; 171mg; 172mg; 173mg; 174mg; 175mg; 176mg; 177mg; 178mg; 179mg; 180mg; 181mg; 182mg; 183mg; 184mg; 185mg; 186mg; 187mg; 188mg; 189mg; 190mg; 191mg; 192mg; 193mg; 194mg; 195mg; 196mg; 197mg; 198mg; 199mg; 200mg; 0.01mg to 1mg; 0.1mg to 1mg; 1 to 200mg; 1 to 100mg; 1 to 50mg; 1 to 25mg; 1 to 15mg; 1 to 10mg; 10 to 100mg; 10 to 75mg; 10mg to 50mg; and 10mg to 25mg. [0019] Preferably, the biologically active material is present in the composition at a quantity selected from the group consisting of: 0.01mg; 0.1mg; 1mg; 2mg; 5mg; 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg. [0020] Preferably, the biologically active material is present in the composition at a quantity selected from the group consisting of: semaglutide 15mg; liraglutide 21mg; dulaglutide 10mg; exenatide 2mg; and lixisenatide 20mg. [0021] Preferably, the biologically active material is present in the composition at a quantity selected from the group consisting of: dapagliflozin 10mg; empagliflozin 25mg; and ertugliflozin 5mg. [0022] Preferably, the composition comprises one or more agents selected from the group consisting of: an entero-hepatic recycling agent; an absorption agent; a bile salt; a penetrant; a surfactant; an ionic water soluble post-disintegration viscosity agent; a mucolytic (mucus buster); a mucoadhesive; an adjuvant; a disintegration viscosity agent; a permeation enhancer; an absorption enhancer; and a entero-hepatic-biliary recirculation agent. [0023] Preferably, the entero-hepatic recycling agent is selected from the group consisting of: glycodeoxycholate; glycocholate; taurocholate; glycolithocholate; glycohyocholate; tauroursodeoxycholate; taurohyodeoxycholate; and salts thereof. [0024] Preferably, the composition comprises a plurality of entero-hepatic recycling agents. [0025] Preferably, the entero-hepatic recycling agent is selected from the group consisting of: sodium glycodeoxycholate; and sodium deoxycholate. [0026] Preferably, the concentration of the entero-hepatic recycling agent is selected from the group consisting of: 0.01%; 0.5%; 1%; 0.5%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; and within 2 decimal points of each figure (w/w). [0027] Preferably, the entero-hepatic recycling agent(s) are bile salts and soy lecithin. [0028] Preferably, the entero-hepatic recycling agent(s) are permeation enhancers. [0029] Preferably, the entero-hepatic recycling agent(s) open tight junctions in the sublingual/gastro-intestinal mucosa cells. [0030] Preferably, the entero-hepatic recycling agent(s) influence the integrity of tight junctions between epithelial cells and modulate these tight junctions, allowing for an increased in paracellular transport. [0031] Preferably, the entero-hepatic recycling agent(s) improve/enhance the absorption of lipophilic compounds as they can interact with both lipophilic drugs and the lipids present in cell membranes [0032] Preferably, the entero-hepatic recycling agent(s) and the glucagon-like peptide 1 (GLP-1) agonist form a complex. [0033] Preferably, the entero-hepatic recycling agent(s) and the glucagon-like peptide 1 (GLP-1) agonist form a complex which has a particle size less than 2000nm. [0034] Preferably, the entero-hepatic recycling agent(s) and the glucagon-like peptide 1 (GLP-1) agonist form a complex which is absorbed into the blood circulation and metabolised into the active glucagon-like peptide 1 (GLP-1) agonist improving the bioavailability of the glucagon-like peptide 1 (GLP-1) agonist. [0035] Preferably, the ionic water soluble post-disintegration viscosity agent is selected from the group consisting of: carboxymethyl cellulose; anionic substituted cellulose or starch derivatives, such as salts of carboxymethyl celluloses (CMC), alginate and starch glycolates. [0036] Preferably, the ionic water soluble post-disintegration viscosity agent is carboxymethyl cellulose. [0037] Preferably, the ionic water soluble post-disintegration viscosity agent is at a concentration selected from the group consisting of: 1%; 0.5%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; and within 2 decimal points of each figure (w/w). [0038] Preferably, the disintegration viscosity agent is sodium alginate. [0039] Preferably, the disintegration viscosity agent is at a concentration selected from the group consisting of: 1%; 0.5%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; and within 2 decimal points of each figure (w/w). [0040] Preferably, the composition comprises a permeation enhancer. Preferably, the permeation enhancer is SNAC (salcaprozate sodium). Preferably, the permeation enhancer is a non-ionic ester alkoxylate or an alkanoic acid ester alkoxylate. Examples of non-ionic ester alkoxylates are selected from the group consisting of: sorbitan fatty acid esters (Spans); polysorbates (Tweens). Preferably, the alkanoic acid ester alkoxylate is selected from the group consisting of: vitamin E ethoxylated derivatives; tocopherol succinate ethoxylate (TPGS); tocofersolan; and ethoxylated phytosterol. [0041] Preferably, the permeation enhancer is SNAC (salcaprozate sodium) and is surfactant-like structurally and has the ability to chaperone poorly-permeable macromolecules across plasma membranes via a transcellular mode of action and helps sublingual absorption of peptides. [0042] Preferably, the SNAC (salcaprozate sodium) and the glucagon-like peptide 1 (GLP-1) agonist form a complex. Preferably, the non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) and the glucagon-like peptide 1 (GLP-1) agonist form a complex. [0043] Preferably, the permeation enhancer is at a concentration selected from the group consisting of: 0%; 0.05%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%, 30%, 40%; and within 2 decimal points of each figure (w/w). [0044] Preferably, the permeation enhancer is at a quantity selected from the group consisting of: 5mg; 10mg; 25mg; 30mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg. [0045] Preferably, the permeation enhancer protects the glucagon-like peptide 1 (GLP- 1) agonist against the effects of pepsin (primary digestive enzymes in the stomach which digest/convert protein and peptides to amino acids). [0046] Preferably, the composition comprises a glucagon-like peptide 1 (GLP-1) agonist-cholate-SNAC-sodium glucose co-transporter-2 (SGLT-2) receptor antagonist cluster or glucagon-like peptide 1 (GLP-1) agonist-cholate-non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate)-sodium glucose co- transporter-2 (SGLT-2) receptor antagonist cluster. [0047] Preferably, the composition comprises a semaglutide-cholate-SNAC- dapagliflozin cluster or semaglutide-cholate-non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate)-dapagliflozin cluster [0048] Preferably, the composition is formulated to pH 5-7.5 to inhibit pepsin activity. [0049] Preferably, the composition is formulated to pH 5-8.0 to inhibit pepsin activity. [0050] Preferably, the entero-hepatic-biliary recirculation agent is soy lecithin. [0051] Preferably, the entero-hepatic-biliary recirculation agent is soy lecithin. [0052] Preferably, the entero-hepatic-biliary recirculation agent is at a concentration selected from the group consisting of: 0.05%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%, 30%, 40%; and within 2 decimal points of each figure (w/w). [0053] Preferably, the entero-hepatic-biliary recirculation agent is at a quantity selected from the group consisting of: 5mg; 10mg; 25mg; 30mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg. [0054] Preferably, the entero-hepatic-biliary recirculation agent provides absorption enhancement. [0055] Preferably, the entero-hepatic-biliary recirculation agent provides absorption enhancement using factors selected from the group consisting of: a local alteration in the membrane structure and modification of its permeability; bioadhesion to the mucosa surfaces; and the lowering of the mucociliary clearance. [0056] Preferably, the composition comprises a mucoadhesive polymer, with a mucolytic property to break the GI/oro-mucosal mucus layer/barrier for bioactive penetration. [0057] Preferably, the composition comprises one or more agents selected from the group consisting of; sodium glycodeoxycholate; sodium deoxycholate; carboxymethyl cellulose; sodium alginate; SNAC (salcaprozate sodium); non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate); and soy lecithin. [0058] Preferably, the composition comprises one or more biologically active materials and agents selected from Table 1 or Table 2. [0059] Preferably, the composition has a pH selected from the group consisting of: between 5 to 6; between 4 to 7.5; between 6 to 7.5; between 7.0 – 7.5; and between 7.0 – 8.0. [0060] Preferably, the composition is a solid. Preferably, the composition is lyophilised. [0061] Preferably, the particles of the composition have a size no greater than 2000 nm. [0062] Preferably, the particles of the composition have a nanoparticulate size. [0063] Preferably, the composition comprises further pharmaceutically acceptable additives and agents. [0064] Preferably, the composition comprises a pharmaceutically acceptable buffering reagent. [0065] Preferably, the buffering reagent is selected from the group consisting of: salts of phosphates, carbonates, Tris; preferably combinations of phosphate salts; including sodium carbonate. [0066] Preferably, the buffering reagent is present at a concentration selected from the group consisting of: 0.1-0.5%; 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; and within 2 decimal points of each figure (w/w). [0067] Preferably, the wafers are buffered with a suitable buffer, most preferably a blend of mono- and di-alkaline salt phosphates, adjusted to afford a pH optimal for the stability of the chosen biological active, generally between 4 and 7.5. [0068] Preferably, the wafers are buffered with a suitable buffer, most preferably a blend of mono- and di-alkaline salt phosphates, adjusted to afford a pH optimal for the stability of the chosen biological active, generally between 4 and 8.0. [0069] Preferably, the composition comprises a colouring agent. [0070] Preferably, the composition comprises a flavouring agent. [0071] Preferably, the composition comprises a stability agent. [0072] Preferably, the stability agent is selected from the group consisting of: metal chelators such as EDTA, pharmaceutically acceptable surfactant including polysorbate 80. [0073] Preferably, the composition is a glucagon-like peptide 1 (GLP-1) agonist bile salt- lecithin complex. [0074] Preferably, the composition is a glucagon-like peptide 1 (GLP-1) agonist bile salt- lecithin-SNAC (salcaprozate sodium) complex. Preferably, the composition is a glucagon-like peptide 1 (GLP-1) agonist bile salt-lecithin-non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex. [0075] Preferably, the composition comprises a complex selected from the group consisting of: glucagon-like peptide 1 (GLP-1) agonist - bile salt - lecithin complex; glucagon- like peptide 1 (GLP-1) agonist - bile salt – lecithin - SNAC (salcaprozate sodium) complex; glucagon-like peptide 1 (GLP-1) agonist - entero-hepatic recycling agent(s) complex; glucagon-like peptide 1 (GLP-1) agonist - SNAC (salcaprozate sodium) complex; glucagon- like peptide 1 (GLP-1) agonist - entero-hepatic recycling agent(s) - SNAC (salcaprozate sodium) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt - lecithin complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - SNAC (salcaprozate sodium) complex; a sodium glucose co-transporter-2 (SGLT- 2) receptor antagonist - entero-hepatic recycling agent(s) complex; a sodium glucose co- transporter-2 (SGLT-2) receptor antagonist - SNAC (salcaprozate sodium) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - SNAC (salcaprozate sodium) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt - lecithin complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - SNAC (salcaprozate sodium) complex; glucagon- like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - SNAC (salcaprozate sodium) complex; and glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - SNAC (salcaprozate sodium) complex. [0076] Preferably, the composition comprises a complex selected from the group consisting of: glucagon-like peptide 1 (GLP-1) agonist - bile salt - lecithin complex; glucagon- like peptide 1 (GLP-1) agonist - bile salt – lecithin - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; glucagon-like peptide 1 (GLP-1) agonist - entero-hepatic recycling agent(s) complex; glucagon-like peptide 1 (GLP- 1) agonist - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; glucagon-like peptide 1 (GLP-1) agonist - entero-hepatic recycling agent(s) - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt - lecithin complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt - lecithin complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co- transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex; and glucagon- like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) (or alkanoic acid ester alkoxylate) complex. [0077] Preferably, the composition disintegrates once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s (seconds). [0078] Preferably, the composition disintegrates once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s; <130s; <140s; <150s; <160s; <170s; <180s; <190s; <200s; <210s; <220s; <230s; <240s; <250s; <260s; <270s; <280s; <290s; <300s; <310s; <320s; <330s; <340s; <350s; <360s; <370s; <380s; <390s; <400s; <410s; <420s; <430s; <440s; <450s; <460s; <470s; <480s; <490s; <500s; <510s; <520s; <530s; <540s; <550s; <560s; <570s; <580s; <590s; <600s; <610s; <620s; <630s; <640s; <650s; <660s; <670s; <680s; <690s; <700s; <710s; <720s; <730s; <740s; <750s; <760s; <770s; <780s; <790s; <800s; <810s; <820s; <830s; <840s; <850s; <860s; <870s; <880s; <890s; <900s; <900s; <930s; <960s; <990s; <1020s; <1050s; <1080s; <1110s; <1140s; <1170s; <1200s; <1230s; <1260s; <1290s; <1320s; <1350s; <1380s; <1410s; <1440s; <1470s; <1500s; <1530s; <1560s; <1590s; <1620s; <1650s; <1680s; <1710s; <1740s; <1770s; <1800s; <1830s; <1860s; <1890s; <1920s; <1950s; <1980s; <2010s; <2040s; <2070s; <2100s; <2130s; <2160s; <2190s; <2220s; <2250s; <2280s; <2310s; <2340s; <2370s; <2400s; <2430s; <2460s; <2490s; <2520s; <2550s; <2580s; <2610s; <2640s; <2670s; <2700s; <2730s; <2760s; <2790s; <2820s; <2850s; <2880s; <2910s; <2940s; <2970s; <3000s; <3030s; <3060s; <3090s; <3120s; <3150s; <3180s; <3210s; <3240s; <3270s; <3300s; <3330s; <3360s; <3390s; <3420s; <3450s; <3480s; <3510s; <3540s; <3570s; <3600s; <3630s; <3660s; <3690s; <3720s; <3750s; <3780s; <3810s; <3840s; <3870s; <3900s; <3930s; <3960s; <3990s; <4020s; <4050s; <4080s; <4110s; <4140s; <4170s; <4200s; and <4230s (seconds). [0079] Preferably, the composition disintegrates in the oral cavity without leaving a residue of said dosage form in the oral cavity that is detectable by a subject, thereby avoiding the urge for the subject to swallow the composition. [0080] Preferably, the composition dissolves once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s; 180s, preferably 15-60s (seconds). [0081] Preferably, the composition dissolves once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s; <130s; <140s; <150s; <160s; <170s; <180s; <190s; <200s; <210s; <220s; <230s; <240s; <250s; <260s; <270s; <280s; <290s; <300s; <310s; <320s; <330s; <340s; <350s; <360s; <370s; <380s; <390s; <400s; <410s; <420s; <430s; <440s; <450s; <460s; <470s; <480s; <490s; <500s; <510s; <520s; <530s; <540s; <550s; <560s; <570s; <580s; <590s; <600s; <610s; <620s; <630s; <640s; <650s; <660s; <670s; <680s; <690s; <700s; <710s; <720s; <730s; <740s; <750s; <760s; <770s; <780s; <790s; <800s; <810s; <820s; <830s; <840s; <850s; <860s; <870s; <880s; <890s; <900s; <900s; <930s; <960s; <990s; <1020s; <1050s; <1080s; <1110s; <1140s; <1170s; <1200s; <1230s; <1260s; <1290s; <1320s; <1350s; <1380s; <1410s; <1440s; <1470s; <1500s; <1530s; <1560s; <1590s; <1620s; <1650s; <1680s; <1710s; <1740s; <1770s; <1800s; <1830s; <1860s; <1890s; <1920s; <1950s; <1980s; <2010s; <2040s; <2070s; <2100s; <2130s; <2160s; <2190s; <2220s; <2250s; <2280s; <2310s; <2340s; <2370s; <2400s; <2430s; <2460s; <2490s; <2520s; <2550s; <2580s; <2610s; <2640s; <2670s; <2700s; <2730s; <2760s; <2790s; <2820s; <2850s; <2880s; <2910s; <2940s; <2970s; <3000s; <3030s; <3060s; <3090s; <3120s; <3150s; <3180s; <3210s; <3240s; <3270s; <3300s; <3330s; <3360s; <3390s; <3420s; <3450s; <3480s; <3510s; <3540s; <3570s; <3600s; <3630s; <3660s; <3690s; <3720s; <3750s; <3780s; <3810s; <3840s; <3870s; <3900s; <3930s; <3960s; <3990s; <4020s; <4050s; <4080s; <4110s; <4140s; <4170s; <4200s; and <4230s (seconds). [0082] Preferably, the composition dissolves in the oral cavity without leaving a residue of said dosage form in the oral cavity that is detectable by a subject, thereby avoiding the urge for the subject to swallow the composition. [0083] Preferably, water is removed from the combined agents by a freeze-drying process to a residual level of 0-10%, preferably 0-5%, most preferably 3-5%. [0084] Preferably, the composition has a porosity profile selected from the group consisting of: the proportion of water removed by lyophilization is 65-75%; and the proportion of water removed by lyophilization is >60%. [0085] Preferably, the composition has a patient weight loss property selected from the group consisting of: between 0.01% and 0.1% weight loss; between 0.01% and 1%; between 0. 1% and 1%; between 0.01% and 0.1%; between 1 and 30%; between 5 and 25%; between 8 and 20%; 0.01%; 0.1%; 1%: 2%: 3%: 4%: 5%: 6%: 7%: 8%: 9%: 10%: 11%: 12%: 13%: 14%: 15%: 16%: 17%: 18%: 19%: 20%: 21%: 22%: 23%: 24%: 25%: 26%: 27%: 28%: 29%: 30% and within 2 decimal points of each figure. [0086] Preferably, the composition has a residual moisture content after lyophilisation selected from the group consisting of: between: 0.01 and 20%; between 0.1 and 10%; between 1 and 5%; 0.01%; 0.02%; 0.03%; 0.04%; 0.05%; 0.06%; 0.07%; 0.08%; 0.09%; 0.10%; 0.01%; 0.02%; 0.03%; 0.04%; 0.05%; 0.06%; 0.07%; 0.08%; 0.09%; 0.10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 11%; 12%; 13%; 14%; 15%; 16%; 17%; 18%; 19%; 20% and within 2 decimal points of each figure. [0087] Preferably, the composition is stable for a time period selected from the group consisting of: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; 7 weeks; 8 weeks; 9 weeks; 10 weeks; 11 weeks; 12 weeks; 13 weeks; 14 weeks; 15 weeks; 16 weeks; 17 weeks; 18 weeks; 19 weeks; 20 weeks; 21 weeks; 22 weeks; 23 weeks; 24 weeks; 25 weeks; 26 weeks; 27 weeks; 28 weeks; 29 weeks; 30 weeks; 31 weeks; 32 weeks; 33 weeks; 34 weeks; 35 weeks; 36 weeks; 37 weeks; 38 weeks; 39 weeks; 40 weeks; 41 weeks; 42 weeks; 43 weeks; 44 weeks; 45 weeks; 46 weeks; 47 weeks; 48 weeks; 49 weeks; 50 weeks; 51 weeks; 52 weeks; 1 month; 2 months; 3 months; 4 months; 5 months; 6 months; 7 months; 8 months; 9 months; 10 months; 11 months; 12 months; 13 months; 14 months; 15 months; 16 months; 17 months; 18 months; 19 months; 20 months; 21 months; 22 months; 23 months; 24 months; 25 months; 26 months; 27 months; 28 months; 29 months; 30 months; 31 months; 32 months; 33 months; 34 months; 35 months; 36 months; 37 months; 38 months; 39 months; 40 months; 41 months; 42 months; 43 months; 44 months; 45 months; 46 months; 47 months; 48 months; 49 months; 50 months; 51 months; 52 months; 53 months; 54 months; 55 months; 56 months; 57 months; 58 months; 59 months; 60 months; 1 month to 12 months; 12 months to 24 months; 12 months to 36 months; 12 months to 48 months; 1 year to 2 years; 1 year to 3 years; and 1 year to 5 years. Preferably, the composition is stable as demonstrated by a potency assay run against a reference biological active material. [0088] In another aspect, the invention is a pharmaceutical composition comprising the composition of the first aspect of the invention together with a pharmaceutical excipient or carrier. [0089] In another aspect, the invention is a dosage form comprising the composition of the first aspect of the invention. [0090] Preferably, the dosage form comprises the biologically active material at a dose selected from the group consisting of: 2mg; 5mg 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg. [0091] Preferably, the dosage form comprises the biologically active material at a dose selected from the group consisting of: semaglutide 15mg; liraglutide 21mg; dulaglutide 10mg; exenatide 2mg; and lixisenatide 20mg. [0092] Preferably, the dosage form comprises the biologically active material at a dose selected from the group consisting of: dapagliflozin 10mg; empagliflozin 25mg; and ertugliflozin 5mg. [0093] Preferably, the dosage form is solid. Preferably, the dosage form is freeze dried. Preferably, the dosage form is a wafer. [0094] In another aspect, the invention is a method of treating or preventing or delaying a disease or disorder, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of one aspect of the invention. [0095] Preferably, the disease or disorder is selected from the group consisting of: appetite suppression; weight loss; weight management; obesity; type 2 diabetes, regulate blood sugar; lower the risk of heart attack, stroke, or death in patients with type 2 diabetes and heart or blood vessel disease; cardiovascular disease; Alzheimer's disease; nonalcoholic steatohepatitis (NASH). [0096] In a preferred embodiment, the dosage form is administered to deliver a therapeutic effective amount of the biological active material. [0097] In a preferred embodiment, the therapeutically effective amount is administered to the subject utilising a dosing regimen selected from the group consisting of: twice hourly; hourly; once every six hours; once every 8 hours; once every 12 hours; once daily; twice weekly; once weekly; once every 2 weeks; once every 6 weeks; once a month; once every 2 months; once every 3 months; once every 4 months; once every 5 months; once every 6 months; once yearly; and once. [0098] Preferably, the dosage form delivers a therapeutic effective amount of the biologically active material. [0099] Preferably, the therapeutically effective amount is an amount of biologically active material selected from the group consisting of: between 0.001 to 100mg/kg; between 2 and 50mg/kg; between 5 and 40mg/kg; between 10 and 30mg/kg; between 20 and 25mg/kg; and 20mg/kg/day. [00100] In a preferred embodiment, the therapeutically effective amount is an amount of biologically active material selected from the group consisting of: 2mg; 5mg 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; 10 to 50mg per dosage event. [00101] Preferably, the therapeutically effective amount is an amount of biologically active material selected from the group consisting of: 2mg; 5mg 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; 10 to 50mg per day. [00102] Preferably, the therapeutically effective amount is administered to the subject using a method selected from the group consisting of: orally; sublingually; buccally. [00103] Preferably, the therapeutically effective amount is administered to the subject using a method selected from the group consisting of: beneath the tongue or buccally. [00104] Preferably, detectable levels of the biologically active material enters the circulation system. [00105] Preferably, the detectable levels of the biologically active material that enters the circulation system is selected from the group consisting of: less than 0.001%; less than 0.01%; less than 0.1%; less than 2%; less than 3%; less than 4%; less than 5%; less than 6%; less than 7%; less than 8%; less than 9%; less than 10%; less than 11%; less than 12%; less than 13%; less than 14%; less than 15%; less than 16%; less than 17%; less than 18%; less than 19%; less than 20%; less than 21%; less than 22%; less than 23%; less than 24%; ess than 25%; less than 26%; less than 27%; less than 28%; less than 29%; less than 30%; less than 31%; less than 32%; less than 33%; less than 34%; less than 35%; less than 36%; less than 37%; less than 38%; less than 39%; less than 40%; less than 41%; less than 42%; less than 43%; less than 44%; less than 45%; less than 46%; less than 47%; less than 48%; less than 49%; less than 50%; less than 51%; less than 52%; less than 53%; less than 54%; less than 55%; less than 56%; less than 57%; less than 58%; less than 59%; less than 60%; less than 61%; less than 62%; less than 63%; less than 64%; less than 65%; less than 66%; less than 67%; less than 68%; less than 69%; less than 70%; less than 71%; less than 72%; less than 73%; less than 74%; and less than 75% (w/w%). [00106] Preferably, said biologically active material is absorbed by diffusion directly into the systemic circulation. [00107] Preferably, said biologically active material is sublingually absorbed rapidly. [00108] Preferably, the drug form is delivered sublingually and more suitable for patients phobic to subcutaneous injection. [00109] Preferably, the sublingual administered glucagon-like peptide 1 (GLP-1) agonist has multiple sites action, that is, initial rapid sublingual absorption, then, those glucagon-like peptide 1 (GLP-1) agonists not absorbed sublingually is swallowed into the stomach which then undergo stomach absorption and finally reaching the small intestine which then react locally in the intestinal and colon mucosa L-cells (enteroendocrine cells which produce and release hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)), a local intrinsic reaction for immediate satiety effect. [00110] Preferably, the released GLP-1 stimulates pancreatic insulin, which helps regulate blood sugar levels and also inhibit glucagon secretion, slowing down gastric emptying, and promote a feeling of satiety or fullness (appetite suppression). [00111] Preferably, the released PYY hormone produced by L-cells helps to reduce appetite, slow down gut motility, and modulate the absorption of nutrients from the intestines. [00112] Preferably, the glucagon-like peptide 1 (GLP-1) agonist -bile salt-lecithin complex undergoes absorption in the small intestine and the absorbed complex undergoes liver first- pass metabolism and the free glucagon-like peptide 1 (GLP-1) agonist secrets back into the small intestine (entero-hepatic recirculation) actively attached onto the L-cells again releasing GLP-1 and PYY resulting in their pharmacological satiety effect, and wherein the parenteral administered semaglutide only has a systemic effect with minimal or no local intestinal/colon mucosa effect. [00113] Preferably, currently oral semaglutide has very low oral bioavailability (0.8 to 1.4%) and may need up to 50 mg per dose to be effective, yet this sublingual semaglutide uses 3 times (15mg versus 50mg) less semaglutide due to its multiple sites of action. [00114] Preferably, there is a correlation between semaglutide tablet erosion and semaglutide plasma exposure and wherein full tablet erosion at 1 hour resulted in very low plasma exposure of semaglutide, whereas less than 54 % tablet erosion resulted in high plasma exposure of semaglutide, hence the mandatory criteria of using less than 120mL of water during oral administration and wherein there is no problem with sublingual administration (no water needed for disintegration, fully disintegrated with saliva). [00115] Preferably, the t½ of the administered glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of: between 15 and 20 min; between 20 and 25 min; between 25 and 30 min; between 30 and 35 min; between 35 and 40 min; between 40 and 45 min; between 45 and 50 min; between 30 and 60 min; between 1 and 2 hrs; between 2 and 3 hrs; between 3 and 4 hrs; between 4 and 5 hrs; between 5 and 6 hrs; between 6 and 12 hrs; between 12 and 24 hrs; between 1 and 2 days; between 2 and 3 days; between 3 and 4 days; between 4 and 5 days; between 5 and 6 days; between 6 and 7 days; between 6 and 7 days; between 1 and 2 weeks; between 2 and 3 weeks; between 3 and 4 weeks; between 1 and 2 months; between 2 and 3 months; between 3 and 4 months; between 4 and 5 months; between 5 and 6 months; between 6 and 12 months; and between 1 and 2 years. [00116] In a preferred embodiment, the t½ of the administered glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of: between 30 and 40 min. [00117] In a preferred embodiment, the t½ of the administered glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of: 33 min; 34 min; 35 min; 36 min; 38 min; between 30 and 40 min. [00118] In a preferred embodiment, the t½ of the administered semaglutide is selected from the group consisting of: 33 min; 34 min; 35 min; 36 min; 38 min; between 30 and 40 min. [00119] In another aspect, the invention is a method of appetite suppression, weight loss and/or weight management, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of one aspect of the invention. [00120] Use of the composition of the first aspect of the invention in the manufacture of a medicament for the treatment or prevention of a disease or disorder. [00121] In another aspect, the invention is a process of preparing the composition of the first aspect of the invention, said process comprising the steps of: (1) combining at least one matrix forming agent with a biological active material to form a mixture; and (2) freeze drying the mixture to form the solid dosage form. [00122] In another aspect, the invention is a kit comprising the dosage form of one aspect of the invention together with instructions for its use. [00123] In a preferred embodiment, the kit is directed to treating of preventing a disease or disorder selected from the group consisting of: appetite suppression; weight loss; weight management; obesity; type 2 diabetes, regulate blood sugar; lower the risk of heart attack, stroke, or death in patients with type 2 diabetes and heart or blood vessel disease; cardiovascular disease; Alzheimer's disease; nonalcoholic steatohepatitis (NASH). [00124] Further features of the present invention are more fully described in the following description of several non-limiting embodiments thereof. This description is included solely for the purposes of exemplifying the present invention. It should not be understood as a restriction on the broad summary, disclosure or description of the invention as set out above. Brief Description of the Drawings [00125] Below is a brief description of each of the figures and drawings. [00126] Figure 1 shows the pH dependence of semaglutide solubility. [00127] Figure 2 shows the chemical structure of semaglutide. [00128] Figure 3 shows the chemical structure of deoxycholate sodium. [00129] Figure 4 shows the chemical structure of SNAC. [00130] Figure 5 shows the chemical structure of dapagliflozin. [00131] Figure 6 shows a schematic diagram of the semaglutide + cholate + SNAC + dapagliflozin cluster. [00132] Figure 7 shows a schematic diagram of the process of semaglutide/dapagliflozin delivery via the gastrointestinal tract. [00133] Figure 8 supplements Figure 7 and shows an expanded region of Figure 7, and, in particular, the entero-hepatic-biliary system. [00134] Figure 9 shows a graph of the single dose pharmacokinetic study in Sprague- Dawley rats. Detailed Description of the Invention [00135] For convenience, the following sections generally outline the various meanings of the terms used herein. Following this discussion, general aspects regarding compositions, use of medicaments and methods of the invention are discussed, followed by specific examples demonstrating the properties of various embodiments of the invention and how they can be employed. [00136] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. The invention includes all such variations and modifications. The invention also includes all of the steps, features, formulations and compounds referred to or indicated in the specification, individually or collectively and any and all combinations or any two or more of the steps or features. [00137] Each document, reference, patent application or patent cited in this text is expressly incorporated herein in their entirety by reference, which means that it should be read and considered by the reader as part of this text. That the document, reference, patent application or patent cited in this text is not repeated in this text is merely for reasons of conciseness. None of the cited material or the information contained in that material should, however, be understood to be common general knowledge. [00138] Manufacturer’s instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated herein by reference, and can be employed in the practice of the invention. [00139] The invention described herein may include one or more ranges of values (e.g., size, concentration etc.). A range of values will be understood to include all values within the range, including the values defining the range, and values adjacent to the range that lead to the same or substantially the same outcome as the values immediately adjacent to that value which defines the boundary to the range. [00140] The present invention is not to be limited in scope by any of the specific embodiments described herein. These embodiments are intended for the purpose of exemplification only. Functionally equivalent products, formulations and methods are clearly within the scope of the invention as described herein. 1. DEFINITIONS – [00141] The meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail. [00142] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term "about." The term "about" when used in connection with percentages can mean ±1%. [00143] The invention described herein may include one or more range of values (e.g., size, concentration etc.). A range of values will be understood to include all values within the range, including the values defining the range, and values adjacent to the range which lead to the same or substantially the same outcome as the values immediately adjacent to that value which defines the boundary to the range. For example, a person skilled in the field will understand that a 10% variation in upper or lower limits of a range can be totally appropriate and is encompassed by the invention. More particularly, the variation in upper or lower limits of a range will be 5% or as is commonly recognised in the art, whichever is greater. [00144] In this application, the use of the singular also includes the plural unless specifically stated otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, the use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. Also, terms such as “element” or “component” encompass both elements and components comprising one unit and elements and components that comprise more than one subunit unless specifically stated otherwise. Also, the use of the term “portion” can include part of a moiety or the entire moiety. [00145] Throughout this specification, unless the context requires otherwise, the word "comprise" or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. [00146] “Therapeutically effective amount” as used herein with respect to methods of treatment and in particular drug dosage, shall mean that dosage that provides the specific pharmacological response for which the drug is administered in a significant number of subjects in need of such treatment. It is emphasized that “therapeutically effective amount,” administered to a particular subject in a particular instance will not always be effective in treating the disorder, condition of diseases described herein, even though such dosage is deemed a “therapeutically effective amount” by those skilled in the art. It is to be further understood that drug dosages are, in particular instances, measured as sublingual, oro- mucosal, or oral dosages, or with reference to drug levels as measured in blood. Amounts effective for such a use will depend on: the desired therapeutic effect; the potency of the biologically active material; the desired duration of treatment; the stage and severity of the disease being treated; the weight and general state of health of the patient; and the judgment of the prescribing physician. Treatment dosages need to be titrated to optimize safety and efficacy. One skilled in the art will appreciate that the appropriate dosage levels for treatment will thus vary depending, in part, upon the indication for which the active agent is being used, the route of administration, and the size (body weight, body surface or organ size) and condition (the age and general health) of the patient. Accordingly, the clinician may titre the dosage and modify the route of administration to obtain the optimal therapeutic effect. A typical dosage may range from about 0.1 ^g/kg to up to about 100 mg/kg or more, depending on the factors mentioned above. In other embodiments, the dosage may range from 0.1 ^g/kg up to about 100 mg/kg; or 1 ^g/kg up to about 100 mg/kg; or 5 ^g/kg up to about 100 mg/kg. [00147] The frequency of dosing will depend upon the pharmacokinetic parameters of the active agent and the formulation used. Typically, a clinician will administer the composition until a dosage is reached that achieves the desired effect. The composition may therefore be administered as a single dose, or as two or more doses (which may or may not contain the same amount of the desired molecule) over time, or as a continuous infusion via an implantation device or catheter. Further refinement of the appropriate dosage is routinely made by those of ordinary skill in the art and is within the ambit of tasks routinely performed by them. Appropriate dosages may be ascertained through use of appropriate dose- response data. [00148] As used herein "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. [00149] As used herein the term “subject” generally includes mammals such as: humans; farm animals such as sheep, goats, pigs, cows, horses, llamas; companion animals such as dogs and cats; primates; birds, such as chickens, geese and ducks; fish; and reptiles. The subject is preferably human. In one embodiment, the human subject is an infant, child, or adolescent. In one embodiment, the human subject is a paediatric patient aged 21 or younger at the time of their diagnosis or treatment. [00150] Other definitions for selected terms used herein may be found within the detailed description of the invention and apply throughout. Unless otherwise defined, all other scientific and technical terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the invention belongs. [00151] Features of the invention will now be discussed with reference to the following non-limiting description and examples. 2. EMBODIMENTS [00152] The inventors have developed a sublingual, oromucosal and oral deliverable semaglutide formulation. In one embodiment, by combining dapagliflozin and semaglutide with different pharmacological action, we have provided an improved weight loss effect. [00153] The added advantage of sublingual, oromucosal and oral semaglutide is the targeted local pharmacological effect when taken orally making semaglutide more suitable for oral therapeutic use than subcutaneous injection. Most importantly, the sublingual, oromucosal and/or orally administered semaglutide has a double action, that is, to react locally sublingually and in the intestinal and colon mucosa (local effect) for immediate satiety effect as well as when absorbed into the blood stream have a systemic effect similar to subcutaneous injection; a two prong pharmacological activities (local as well as parenteral effects unlike injection which only have parenteral effect and no local intestinal/colon mucosa effect). [00154] Currently, semaglutide is available as a subcutaneous injection preparation approved for treatment of type 2 diabetes mellitus and obesity plus one oral tablet preparation approved for the treatment of type 2 diabetes mellitus. Semaglutide is less suitable for oral administration due to its very low oral bioavailability (less than 0.1%). The approved oral tablet semaglutide formulation has an oral bioavailability of 0.4 to 1% via stomach absorption. Semaglutide is also easily damaged by the stomach’s gastric acid, digestive enzymes and intestinal mucosa barrier to absorption by passive diffusion against macromolecules penetration leading to poor absorption and low bioavailability. [00155] Administration of a semaglutide wafer is a non-invasive procedure and is only taken once a day, is convenient with a better compliance instead of the invasive daily subcutaneous injection. Improving the absorption of semaglutide in the intestine/colon can be challenging since it is a peptide-based drug that can be susceptible to acid degradation. Hence, we have invented a novel wafer which enhances the absorption of semaglutide, plus neutralising the hostile gastric environment and allowing some stomach absorption of semaglutide and transporting it onto the small intestine and colon where the absorption takes place. Our novel formulation techniques improve the water solubility (enhanced absorption via active uptake) and improves the stability of semaglutide, using nanoparticle complexes, and vehicles that protect the drug from hostile acidic stomach and pepsin enzyme degradation. [00156] This is the first semaglutide sublingual, oromucosal and/or oral wafer preparation and the first to have multiple pharmacological actions: (1) First, immediate sublingual semaglutide absorption circulating into the brain satiety centre; (2) The unabsorbed sublingual semaglutide flows into the stomach via the physiological saliva flow and undergoes some stomach absorption, increasing the systemic blood concentration of semaglutide; (3) The remaining unabsorbed semaglutide in the stomach then flows into the small intestine, rapidly activates the nerve receptors in the intestinal epithelia cells, a local reaction sending signal to the satiety centre located in the ventromedial hypothalamus in the brain; (4) The remaining semaglutide-bile salts-lecithin complexes are actively absorbed into the intestinal mucosa and metabolised to free semaglutide, lecithin and bile salts by the liver. The free semaglutide released into the small intestine (enterohepatic recirculation) then stimulate the L-cells to release native GLP-1 hormone (intrinsic effect) which also acts on the satiety centre of the brain (hence a dual action by GLP-1 hormone and the GLP-1 analogue peptide semaglutide). [00157] In one embodiment, the inventors have formulated a novel oral formulation of semaglutide (a GLP-1 analogue polypeptide) with the following advantages. Addition of permeation and absorption enhancers to improve the transport of semaglutide across the intestinal epithelium. These substances can temporarily disrupt the integrity of the intestinal barrier, allowing for enhanced drug absorption. Absorption enhancers include surfactants, bile salts, and certain polymers, thereby improving bioavailability. The permeation absorption enhancers utilized in this oral formulation form a novel micellar, vesicular and polymer-based nano-particles therapeutic systems, a simple derivatization procedure, turning into attractive building blocks for the oral delivery of semaglutide and other biologics with absorption-enhancing activity. Withstand the gastrointestinal impediments by preventing the peptide degradation in the acid stomach and effectively reach the small intestines maintaining its stability and potency, where semaglutide peptide can then exert its local effects in the small intestine and colon. Aid in the active transporter-mediated absorption of semaglutide via the paracellular and transcellular cells absorption as well as via the tight- junction mucosa cells. Binding of semaglutide to the nuclear-receptors present in the intestinal mucosal cell surfaces which then activate transcriptional networks, which then effect the expression of a number of target genes, including those for membrane transport proteins improving the bioavailability of semaglutide. Create micellar solubilization with nanoparticles below 200nm influencing and improving the semaglutide and the easy transport across the intestinal mucosa membranes. The absorption enhancer-semaglutide is ion-pairing and the formed complexes may have either higher or lower polarity compared to the drug molecule itself, which changes its physicochemical and pharmacokinetic properties. The further incorporation of enzyme inhibitors as well as a mucoadhesive polymer in the oral dosage forms is also further contributed to an improvement of an oral bioavailable active form of polypeptide semaglutide macromolecular drugs, with effective protection and absorption enhancement properties. Composition [00158] The composition of the present invention comprises at least one matrix forming agent. In the freeze-dried systems of the prior art, gelatin is the most commonly used carrier or structure forming agent due to its wall-forming ability. Gelatin is an ionic water soluble polymer, and as such, when mixed with active pharmaceutical ingredients in water; the increasing viscosity of the solution over time may cause a decreasing solubility of poorly soluble drugs in the mixture, and lead to a suspension of the drug in gelatin matrix. This can cause phase separation to occur; and the drug in amorphous or crystalline forms may not be homogenously dispersed in the matrix, which will eventually affect the dissolution and absorption of the final product. [00159] Applicant has found that other polymer materials suitable for forming a matrix may be selected for specific application in the field of drug delivery, especially for site- specific drug delivery system such as in the oral cavity. Matrix forming agents of the present invention may be selected from the group consisting of: non-mammalian gelatin, dextrin, soy protein, wheat protein, psyllium seed protein, acacia gum, guar gum, agar gum, xanthin gum, polysaccharides; alginates; sodium carboxymethylcellulose; carrageenans; dextrans; pectins; sugars; amino acids; starch; modified starches; carboxymethylcellylose; hydroxypropylmethylcellulose; hydroxypropyl cellulose and methyl cellulose inorganic salts; synthetic polymers; amylopectin, polypeptide/protein or poly-saccharide complexes. Examples of at least one matrix forming agent that are carbohydrates include mannitol, dextrose, lactose, galactose, sorbitol and trehalose and cyclodexrin. Examples of matrix forming agents that are inorganic salts may be selected from the group consisting of: sodium phosphate, sodium chloride and aluminium silicates. The at least one matrix forming agent may also be an amino acid. Examples of suitable amino acids include glycine, L-alanine, L- aspartic acid, L-glutamic acid, L-hydroxyproline, L-isoleucine, L-leucine and L-phenylalanine. [00160] In a highly preferred embodiment, at least one matrix forming agent is sodium carboxymethylcellulose. When at least one matrix forming agent is sodium carboxymethyl cellulose, the polymer is present in a concentration of from about 0.1% to about 19% by dry weight of the solid dosage form. In a preferred embodiment the sodium carboxymethylcellulose is present in an amount of about 0.1% to about 15% by dry weight of the dosage form. In a highly preferred embodiment of the present invention, the sodium carboxymethyl cellulose is present in an amount of about 0.1 % to about 1.0% by dry weight of the solid dosage form. In another embodiment of the present invention, the dissolving dosage form comprises amylopectin as at least one matrix forming agent. Amylopectin is capable of increasing the release of the biologically active material by promoting formulation disintegration. Amylopectin may be present in the dosage form at a concentration about 2% up to no greater than 20% by dry weight of the solid dosage form. In a highly preferred form of the present invention, amylopectin is present in an amount of about 2% to about 17% dry weight of the dosage form. [00161] To achieve dissolution of drugs, low MW diluents may be added as at least one matrix forming material. Diluents include microcrystalline cellulose (e.g., Avicel PH 101^® and Avicel PH 102^®), lactose, starch and sorbitol. These diluents may be present in the dosage form either alone or as a mixture in different ratios, and may be about 1% to about 80%, preferably about 2% to about 50%, either individually or cumulatively. In one embodiment of the present invention, the dissolving dosage form comprises microcrystalline cellulose as the at least one matrix forming agent. Microcrystalline cellulose may act as a filler and binder in the dosage form of the present invention. Microcrystalline cellulose has the ability to compact with minimum compression pressures, and results in a hard, stable and dissolving dosage form. Due to its large surface area and high internal porosity, microcrystalline cellulose is able to absorb and retain large amounts of water, which is desirable in the dosage form of the invention. When the solid dosage form of the present invention comprises microcrystalline cellulose, it is present in an amount of about 1% to about 10%, and preferably from about 1% to about 8% by dry weight of the dosage form. The effectiveness of the dissolving dosage form of the present invention relies on the drug dissolving in a small volume of fluid, such as in the oral cavity, prior to absorption into the systemic circulation. Therefore, the rate of dissolution of the dosage form is important. In a preferred embodiment of the present invention, the dosage form comprises a super- disintegrant as at least one matrix forming material. [00162] In a highly preferred embodiment, the dissolving dosage form of the present invention comprises glycine. Glycine is an amino acid with excellent wetting properties and is suitable for the dissolving formulation. Low amounts of glycine may be used in the formulation of the present invention to control the dissolution rate of the dosage form. Furthermore, glycine may also be used as an anti-collapsing agent, which maintains the dosage form from shrinking either during the manufacture process or after packing. In one embodiment, the dosage form of the present invention comprises from about 0.5% to about 5% dry weight of the dosage form. According to another embodiment of the invention, the solid dosage form may include a matrix forming agent such as mannitol. Mannitol is a component that may aid in the crystalline structure and impart hardness of the dosage form. When mannitol is present in the dosage form, it occurs in a concentration of from about 5% to about 80%, and preferably from about 10% to about 60% by dry weight of the dosage form. [00163] In addition, the dissolving dosage form of the present invention may include lubricants, such as polyethylene glycol (PEG) 1000, 1500, 2000, 4000 and 6000, sodium lauryl sulphate, fats or oils. One advantage of the use of these lubricants is to aid in the removal of the dosage form from the mould. These lubricants may be present in the dosage form either alone or as a mixture in different ratios, and may be between 0.05% to 5%, preferable between 0.1% and 2%, preferable about 1.5%, either individually or cumulatively. In one embodiment, the composition includes between 0.05% to 5% polyethylene glycol 1500, preferably between 0.1% and 2% by dry weight of the dosage form, or as mixtures of the various glycols. The invention extends, in another aspect thereof, to improve sublingual absorption of weak base compounds, the composition comprising a solid buffer reagent that affords to produce a saliva pH of 4-6 when dissolved in oral cavity. Increasing the pH of the solution of a weak base compound can increase the ratio of unionized to ionized, which will lead to enhanced sublingual absorption. The solid buffer reagent include sodium dihydrogen phosphate dihydrate, sodium hydrogen phosphate, sodium hydrogen carbonate and sodium carbonate, which may be present in the dosage form either alone or as a mixture in different ratios in a concentration of about 0.01% to about 10% by weight of the composition. Preferably, the buffer reagent is sodium carbonate, which may be present in a concentration of about 0.01% to about 10% by weight of the composition, preferably between 0.1% to 1%, most preferably about 0.3%. [00164] When mannitol is present in the dosage form, it occurs in a concentration of from about 5% to about 80%, and preferably from about 10% to about 60% by dry weight of the dosage form. [00165] The composition may, in certain embodiments, include an absorption enhancer. The absorption enhancer may be a polysaccharide and may be positively charged. Preferably, the absorption enhancer is β-cyclodextrin or its derivatives. The β-cyclodextrin or derivative may be present in a concentration of from about 0.01% to about 10% by dry weight of the dosage form, preferably between 0.2% to 2%, and most preferably about 1 %. The solid dosage form of the present invention may comprise flocculating agents to maintain disbursement of the biologically active material evenly dispersed in the matrix during the manufacture process. The flocculating agent may be gums. Preferably, the gum is xanthan gum. The xanthan gum may be present in a concentration of about 0.01% to about 10% by dry weight of the composition, preferably from about 0.2% to 2%, and most preferably about 1%. [00166] To aid dissolution of the biologically active material into the aqueous environment, a surfactant may be added to the solution as a wetting agent. Suitable surfactants include anionic detergents such as sodium lauryl sulfate, dioctyl sodium sulfosuccinate and dioctyl sodium sulfonate. Cationic detergents may be used and include benzalkonium chloride or benzethomium chloride. The list of possible non-ionic detergents includes lauromacrogol 400, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil 10, 50 and 60, glycerol monostearate, Polysorbate 40, 60, 65 and 80, sucrose fatty acid ester, methyl cellulose and carboxymethyl cellulose. These surfactants may be present in the dosage form either alone or as a mixture in different ratios. Additives which potentially enhance uptake of the compounds are fatty acids such as oleic acid, linoleic acid and linolenic acid. [00167] In order to enhance the aesthetic and taste appeal of the dissolving dosage form to the subject, the dosage form may also contain colouring agents, such as FD & C dyes Blue No. 2 and Red No. 40; flavoring agents, such as orange, mixed berry, cherry, peppermint, raspberry and caramel; and/or sweeteners such as aspartame, stevia, sucralose and saccharin. [00168] The solid dosage form of the present invention is suitable for oral administration to a subject. As discussed above, the dosage form comprises biologically active material. The biologically active material is therefore delivered to the subject via the oral cavity mucosa and into the systemic blood system within a relatively short period of time. In a preferred embodiment, an effective plasma concentration of the biologically active material is reached within a period of no more than two hours, preferably within 30 minutes, and most preferably within 10 minutes. [00169] Furthermore, an advantage of the present invention is that the solid dosage form completely dissolves within 2 seconds to 60 seconds, preferably 2 seconds to 30 seconds, and most preferably within 2 seconds to 10 seconds after administration of the dosage form. In a highly preferred embodiment of the present invention, there is no residue remaining of the dosage form of the present invention after administration that is detectable by the patient. As such, the subject has no urge to swallow the dosage form. [00170] The subject receiving the dissolving dosage form of the present invention may be an animal or human being. When the subject is a human being, it may be an adult or a child, including elderly adults and infants. In particular, the subject is a subject that is unable to or has difficulties in swallowing. [00171] The solid dosage form may comprise sodium carboxymethylcellulose as a formulation aide in low levels. When the amount of sodium carboxymethylcellulose is between about 0.1% and 15% by dry weight of the dosage form, the wafer releases the active agent, without leaving a residue in the oral cavity. In addition, the use of gelatin was avoided by the inventors, and therefore prevents the unwanted residue left in the oral cavity after administration. The addition of lactose and or mannitol was also found to be advantageous in the dosage formulation of the present invention. [00172] Thus, in one embodiment, the present invention provides a solid dosage form adapted for the release of biologically active material in the oral cavity wherein the dosage form comprises: (I) biologically active material and (ii) at least one matrix forming agent, wherein the dosage form substantially dissolves in the oral cavity, wherein the dosage form comprises 0.1-0.3% sodium carbonate, 0.1-4% sodium carboxymethylcellulose, 0.1-10% PEG 1500, 1-4%% glycine, 1-10%% microcrystalline cellulose; 2-17% amylopectin, 10-30% lactose and 30-50% mannitol as a dry weight of the solid dosage form, and which does not result in substantial detectable levels of residue left over in the oral cavity of the patient. Pharmaceutical Compositions [00173] The present invention also provides a pharmaceutical composition comprising the composition of the invention together with a pharmaceutically acceptable carrier. [00174] Therapeutic compositions are within the scope of the present invention. Preferably the compositions are combined with a pharmaceutically acceptable carrier or diluent to produce a pharmaceutical composition (which may be for human or animal use). Suitable carriers and diluents include isotonic saline solutions, for example phosphate- buffered saline. As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. See, e.g., Remington's Pharmaceutical Sciences, 2th Ed. (1995, Mack Publishing Co., Easton, Pa.) which is herein incorporated by reference. [00175] The pharmaceutical composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, colour, isotonicity, odour, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. Suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulphite or sodium hydrogen-sulphite, Vitamin E, Vitamin E phosphate – lipid soluble vitamins, nano emulsions); buffers (such as borate, bicarbonate, tris-HCl, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta- cyclodextrin), fillers; monosaccharides, disaccharides; and other carbohydrates (such as glucose, mannose, or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); colouring, flavouring (natural and natural derived products) and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols – and artificial sweetners (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate 80, triton, tromethamine, lecithin, cholesterol, tyloxapol); stability enhancing agents (sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride), delivery vehicles, diluents, excipients and/or pharmaceutical adjuvants. [00176] The optimal pharmaceutical composition will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format, and desired dosage. Such compositions may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the composition of the invention. The preferred form of the pharmaceutical composition depends on the intended mode of administration and therapeutic application. [00177] The primary vehicle or carrier in a pharmaceutical composition is aqueous and non-aqueous in nature. For example, a suitable vehicle or carrier may be water for injection, physiological saline solution, possibly supplemented with other materials. Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles. Other exemplary pharmaceutical compositions comprise tris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, which may further include sorbitol or a suitable substitute thereof. In one embodiment of the present invention, pharmaceutical compositions may be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents in the form of an aqueous solution and non-aqueous. [00178] The formulation components are present in concentrations that are acceptable to the site of administration. For example, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 (4.5) to about 8 [00179] Additional pharmaceutical compositions will be evident to those skilled in the art, including formulations of the invention in sustained- or controlled-delivery formulations. Techniques for formulating a variety of other sustained- or controlled-delivery means, such as liposome carriers, bio-erodible microparticles or porous beads and depot injections, are also known to those skilled in the art. Additional examples of sustained-sustained-release preparations include semipermeable polymer matrices in the form of shaped articles, for example, films, or microcapsules. Sustained release matrices may include polyesters, hydrogels, polylactides, copolymers of L-glutamic acid and gamma ethyl-L-glutamate, ethylene vinyl acetate or poly-D(-)-3-hydroxybutyric acid. Sustained-release compositions may also include liposomes, which can be prepared by any of several methods known in the art. [00180] The pharmaceutical composition to be used for in vivo administration typically must be sterile. This may be accomplished by filtration through sterile filtration membranes. In addition, the compositions generally are placed into a container having a sterile access port. Once the pharmaceutical composition has been formulated, it may be stored in sterile vials as a solution. [00181] In yet a further preferred embodiment, the composition retains its effective biological activity for a period selected from the group consisting of; greater than 24 hours; greater than 36 hours; and greater than 48 hours. Preferably, the composition is stable for periods selected from the group consisting of: 6 months, 1 year and 2 years. In one example, the composition is stable at temperatures selected from the group consisting of: - 4°C, 4°C, 18°C and 25°C. [00182] As discussed above, the medicaments of the present invention may include one or more pharmaceutically acceptable carriers. The use of such media and agents for the manufacture of medicaments is well known in the art. Except insofar as any conventional media or agent is incompatible with the pharmaceutically acceptable material, use thereof in the manufacture of a pharmaceutical composition according to the invention is contemplated. Pharmaceutical acceptable carriers according to the invention may include one or more of the following examples: [00183] (1 ) surfactants and polymers, including, however not limited to polyethylene glycol (PEG), polyvinylpyrrolidone , polyvinylalcohol, crospovidone, polyvinylpyrrolidone- polyvinylacrylate copolymer, cellulose derivatives, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, carboxymethylethyl cellulose, hydroxypropylmethyl cellulose phthalate, polyacrylates and polymethacrylates, urea, sugars, polyols, and their polymers, emulsifiers, sugar gum, starch, organic acids and their salts, vinyl pyrrolidone and vinyl acetate; and/or [00184] (2) binding agents such as various celluloses and cross-linked polyvinylpyrrolidone, microcrystalline cellulose; and/or (3) filling agents such as lactose monohydrate, lactose anhydrous, microcrystalline cellulose and various starches; and/or [00185] (4) lubricating agents such as agents that act on the increased ability of the dosage form to be ejected from the packaging cavity, and/or [00186] (5) sweeteners such as any natural or artificial sweetener including sucrose, xylitol, sodium saccharin, cyclamate, aspartame, and acesulfame K; and/or [00187] (6) flavouring agents; and/or [00188] (7) preservatives such as potassium sorbate, methylparaben, propylparaben, benzoic acid and its salts, other esters of parahydroxybenzoic acid such as butylparaben, alcohols such as ethyl or benzyl alcohol, phenolic chemicals such as phenol, or quarternary compounds such as benzalkonium chloride; and/or [00189] (8) buffers; and/or [00190] (9) diluents such as pharmaceutically acceptable inert fillers, such as microcrystalline cellulose, lactose, dibasic calcium phosphate, saccharides, and/or mixtures of any of the foregoing; and/or [00191] (10) wetting agents such as corn starch, potato starch, maize starch, and modified starches, croscarmellose sodium, crosspovidone, sodium starch glycolate, and mixtures thereof; and/or [00192] (11) disintegrants; and/or [00193] (12) effervescent agents such as effervescent couples such as an organic acid (e.g., citric, tartaric, malic, fumaric, adipic, succinic, and alginic acids and anhydrides and acid salts), or a carbonate (e.g. sodium carbonate, potassium carbonate, magnesium carbonate, sodium glycine carbonate, L-lysine carbonate, and arginine carbonate) or bicarbonate (e.g. sodium bicarbonate or potassium bicarbonate); [00194] Permeation enhancer; entero-hepatic recycling agent, mucolytic; mucoadhesive, entero-hepatic-biliary recirculation agent such as sodium glycodeoxycholate, sodium deoxycholate, carboxymethyl cellulose, sodium alginate, SNAC (salcaprozate sodium), non- ionic ester alkoxylate (or alkanoic acid ester alkoxylate), soy lecithin etc. and other pharmaceutically acceptable excipients; and/or [00195] (13) other pharmaceutically acceptable excipients. [00196] Medicaments of the invention suitable for use in animals and in particular in human beings typically must be sterile and stable under the conditions of manufacture and storage. The medicaments of the invention comprising biologically active material can be formulated as a solid, a liposome, or other ordered structures suitable to high drug concentration adapted for oral delivery. [00197] In another embodiment, the biologically active material may be combined into a medicament with another biologically active material, or even the same biologically active material. [00198] Medicaments of the invention can be orally, sublingually or oromucosally administered to a subject. Solid dosage forms for oral administration include wafers, but also tablets and capsules. Further, incorporating any of the normally employed excipients, such as those previously listed, and generally 0.1% to 95% of the biologically active material, and more preferably at a concentration of 0.1% to 75% will form a pharmaceutically acceptable non-toxic oral administration. [00199] Dosage forms are within the scope of the invention. In a preferred embodiment, the invention provides a dosage form comprising the composition as described in the first aspect of this invention. [00200] In a further embodiment, the dosage form is a wafer. [00201] Preferably, the dosage form is stored in a sealed and sterile container. Method for treating or preventing [00202] The invention also provides a method of treating a condition, disease or disorder, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of the invention. [00203] In a further preferred embodiment, the dosage form is administered at an amount to at least partially treat the disorder, disease or condition. [00204] In a further preferred embodiment, the therapeutically effective amount is an amount of biologically active material selected from the group consisting of: between 0.001 to 100mg/kg/day; between 1 to 100mg/kg/day; between 2 and 50mg/kg/day; between 5 and 40mg/kg/day; between 10 and 30mg/kg/day; between 20 and 25mg/kg/day; and 20mg/kg/day. Preferably, the therapeutically effective amount is an amount of biologically active material vis selected from the group consisting of: 0.1mg/day; 5mg/day; 10mg/day; 15mg/day; 40mg/day; 400mg/day; 600mg/day; 800mg/day; 1280mg/day; 1500mg/day. [00205] In a further preferred embodiment, therapeutically effective amount is an amount of biologically active material selected from the group consisting of: between 0.01 to 100mg/kg/day; between 1 to 100mg/kg/day; between 2 and 50mg/kg/day; between 5 and 40mg/kg/day; between 10 and 30mg/kg/day; between 20 and 25mg/kg/day; and 20mg/kg/day. Preferably, the therapeutically effective amount is an amount of biologically active material vis selected from the group consisting of: 10mg/day; 15mg/day; 40mg/day; 400mg/day; 600mg/day; 800mg/day; 1280mg/day; 1500mg/day. [00206] In a further preferred embodiment, Tmax occurs between 0.01 and 336 hours; 1 and 4 hours_. [00207] In a further preferred embodiment, T1/2 occurs between 0.11 and 12 hours; 0.01 and 12 hours; 1.1 and 2.4 hours_. [00208] In a further preferred embodiment, the therapeutically effective amount is administered to the subject to treat the disorder. [00209] Preferably the therapeutically effective amount is administered to the subject utilising a dosing regimen selected from the group consisting of: twice hourly; hourly; once every six hours; once every 8 hours; once every 12 hours; once daily; twice weekly; once weekly; once every 2 weeks; once every 6 weeks; once a month; every 2 months; every 3 months; once every 6 months; and once yearly. [00210] Preferably the therapeutically effective amount is administered to the subject using a method selected from the group consisting of: sublingually. [00211] A subject that can be treated with the invention will include humans as well as other mammals and animals. [00212] In a further preferred embodiment, the method comprises administering to a patient in need thereof a therapeutically effective amount of the dosage form of the invention together with an additional active ingredient. In a preferred form, the additional active ingredient is administered using a dosing regimen selected from the group consisting of: at the same time as administering the dosing form of the invention; before administering the dosing form of the invention; after administering the dosing form of the invention; concurrently with administering the dosing form of the invention; sequentially before administering the dosing form of the invention; and sequentially after administering the dosing form of the invention. [00213] Preferably, the additional active ingredient is selected from the group consisting of: a amino acid; a bipeptide; a tripeptide; a polypeptide; an antibody; a small chemical entity. Use of a composition in the manufacture of a medicament [00214] Uses are within the scope of this invention. The invention also provides a use of the composition of the first aspect of the invention in the manufacture of a medicament for the treatment of a condition, disease or disorder. Kit [00215] The invention also provides a kit comprising the dosage form of one aspect of the invention together with instructions for its use. Device [00216] Devices are within the scope of the invention. In a preferred embodiment, the invention provides a device, wherein the device comprises: (1) the composition as described in the first aspect of this invention; and (2) an applicator. Method for stabilising [00217] Methods for stabilizing the composition are within the scope of the invention. [00218] In a further preferred embodiment, the said method protects the composition against degradation. [00219] In yet a further preferred embodiment, the composition retains its effective biological activity for a period selected from the group consisting of; greater than 24 hours; greater than 36 hours; greater than 48 hours; greater than 168 hours. [00220] The addition of approved pharmaceutical excipients to stabilise the composition is preferred from a safety standpoint, as the simpler methodology is likely to produce a less variable outcome and the choice of excipient can be limited to those with Generally Regarded as Safe (GRAS) status. Excipients for the stabilisation of protein solutions can be classified into four broad categories: salts, sugars, polymers or protein/amino acids, based on their chemical properties and mechanism of action. Salts (e.g., chlorides, nitrates) stabilise the tertiary structure of proteins by shielding charges through ionic interactions. Sugars (e.g., glycerol, sorbitol, fructose, trehalose) increase the surface tension and viscosity of the solution to prevent protein aggregation. Similarly, polymers (e.g. polyethylene glycol, cellulose derivatives) stabilise the protein tertiary structure by increasing the viscosity of the solution to prevent protein aggregation and intra- and inter-molecular electrostatic interactions between amino acids in the protein. Proteins (e.g. human serum albumin) are able to stabilise the structure of other proteins through ionic, electrostatic and hydrophobic interactions. Similarly, small amino acids with no net charge, such as alanine and glycine, stabilise proteins through the formation of weak electrostatic interactions. [00221] As discussed above, the medicaments of the present invention may include one or more pharmaceutically acceptable carriers. The use of such media and agents for the manufacture of medicaments is well known in the art. Except insofar as any conventional media or agent is incompatible with the pharmaceutically acceptable material, use thereof in the manufacture of a pharmaceutical composition according to the invention is contemplated. Pharmaceutical acceptable carriers according to the invention may include one or more of the following examples: a. surfactants and polymers, including, however not limited to polyethylene glycol (PEG), polyvinylpyrrolidone , polyvinylalcohol, crospovidone, polyvinylpyrrolidone- polyvinylacrylate copolymer, cellulose derivatives, HPMC, hydroxypropyl cellulose, carboxymethylethyl cellulose, hydroxypropylmethyl cellulose phthalate, polyacrylates and polymethacrylates, urea, sugars, polyols, and their polymers, emulsifiers, sugar gum, starch, organic acids and their salts, vinyl pyrrolidone and vinyl acetate; and/or b. binding agents such as various celluloses and cross-linked polyvinylpyrrolidone, microcrystalline cellulose; and/or (3) filling agents such as lactose monohydrate, lactose anhydrous, microcrystalline cellulose and various starches; and/or c. filling agents such as lactose monohydrate, lactose anhydrous, mannitol, microcrystalline cellulose and various starches; and/or d. lubricating agents such as agents that act on the increased ability of the dosage form to be ejected from the packaging cavity, and/or e. sweeteners such as any natural or artificial sweetener including sucrose, xylitol, sodium saccharin, cyclamate, aspartame, and acesulfame K; and/or f. flavouring agents; and/or g. preservatives such as potassium sorbate, methylparaben, propylparaben, benzoic acid and its salts, other esters of parahydroxybenzoic acid such as butylparaben, alcohols such as ethyl or benzyl alcohol, phenolic chemicals such as phenol, or quarternary compounds such as benzalkonium chloride; and/or h. buffers; and/or i. diluents such as pharmaceutically acceptable inert fillers, such as microcrystalline cellulose, lactose, dibasic calcium phosphate, saccharides, and/or mixtures of any of the foregoing; and/or j. absorption enhancer such as glyceryl trinitrate; k. add penetrants, permeation enhancer; entero-hepatic recycling agent, mucolytic; mucoadhesive, entero-hepatic-biliary recirculation agent such as sodium glycodeoxycholate, sodium deoxycholate, carboxymethyl cellulose, sodium alginate, SNAC (salcaprozate sodium), non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate), soy lecithin Sodium glycodeoxycholate; and/or l. other pharmaceutically acceptable excipients. [00222] Medicaments of the invention suitable for use in animals and in particular in human beings typically must be sterile and stable under the conditions of manufacture and storage. [00223] Methods to produce [00224] According to a further aspect of the present invention, there is provided a method to produce the dosage form of the present invention comprising the steps of combining at least one matrix forming agent with a biological active material to form a mixture and then freeze drying the mixture to form the solid dosage form. In a preferred embodiment of the present invention, the mixture is measured (by weight or volume) into a preformed plastic or aluminium blister mould (individual dose). The blister mould is placed into a freeze dryer for 24 hours and the resultant solid dosage form (wafer) is then sealed with aluminium or plastics foil to prevent moisture absorption. [00225] In one embodiment of the present invention, the method may require that the pH of the mixture is adjusted to a pH within the range of between 3.0 and 10.0, preferably between 6.4 and 7.8. If required, the pH may be adjusted by using an acid, such as hydrochloric acid, phosphoric acid or citric acid; or a basic compound such as sodium hydroxide, sodium dihydrogen phosphate dehydrate, sodium hydrogen phosphate, sodium hydrogen carbonate, tris hydrochloride and sodium carbonate. [00226] In another embodiment, the method may include the step of using a solvent, such as water. If water is used as a solvent, it is preferable to be removed by freeze drying [00227] The invention also provides a composition, methods and processes as described by the foregoing examples. [00228] The present invention will now be described with reference to the following non- limiting Examples. The description of the Examples is in no way limiting on the preceding paragraphs of this specification, however, is provided for exemplification of the methods and compositions of the invention. Examples [00229] It will be apparent to persons skilled in the pharmaceutical arts that numerous enhancements and modifications can be made to the above-described processes without departing from the basic inventive concepts. For example, in some applications the biologically active material may be pretreated and supplied to the process in the pretreated form. All such modifications and enhancements are considered to be within the scope of the present invention, the nature of which is to be determined from the foregoing description and the appended claims. Furthermore, the following Examples are provided for illustrative purposes only, and are not intended to limit the scope of the processes or compositions of the invention. A EXAMPLE 1 – PREPARATION OF PREFERRED COMPOSITION A.1 AIM [00230] The objective is to improve the solubility and bioavailability of the GLP-1 active (<1% for semaglutide) and the solubility of the SGLT-2 active (dapagliflozin is soluble to 1mg/mL in water) with the aim of reducing the dosage levels of one or both of these actives and therefore leading to a reduced side effect profile (side effects may include belching; bloating; excess air or gas in the stomach or intestines; gaseous stomach pain; heartburn; passing gas; recurrent fever; stomach discomfort or pain; sick feeling; feeling thirsty; confused; unusually tired; breathing more deeply or faster). The improved solubility and permeability using surfactants and other excipients “pushes” GLP-1 agonist as well as SGLT-2 antagonists into Class 1 drugs hence increases mucosal absorption. Class I drugs (Biopharmaceutical Classification System or BCS) are generally expected to undergo mucosal absorption more efficiently because they have both high solubility and high permeability. The mucosal surfaces, such as those in the gastrointestinal tract, allow for absorption of substances, and drugs in Class I have characteristics that favor this process with the aim of reducing the dosage. A.2 MATERIALS AND METHODS [00231] The inventors combined a number of molecular properties in a novel manner to deliver molecules of the flozin family of sodium glucose co-transporter-2 (SGLT-2) antagonist (dapagliflozin, empagliflozin, ertugliflozin, canagliflozin, bexaglifloxin and/or glutide or natide family of glucogen-like peptide 1 (GLP-1) (semaglutide, liraglutide, dulaglutide, exenatide, lixisenatide) agonists, individually or in combination, both sublingually into the mucosal bloodstream. As a consequence of the unique protective features described in further details below, these agonists can also be delivered through the absorption in the stomach and intestinal tract. [00232] By way of a background, semaglutide is a moderate MW polypeptide derivative (MW 4113) that has pH-dependent solubility, and several polar and non-polar regions Above pH 7, semaglutide is moderately water soluble, up to 20mg/mL, and poorly soluble below pH7. See Figure 1 from Chen et al., Design and Development of a New Glucagon‑Like Peptide‑1 Receptor Agonist to Obtain High Oral Bioavailability. Pharmaceutical Research (2022) 39:1891–1906) and also Figure 2 for the chemical structure of semaglutide. Developing a protective mechanism against the pH of the surrounding aqueous medium to allow multiple points of absorption orally (pH 5-6), gastrically (pH 1-3) and intestinally (pH 7) would therefore be highly advantageous. [00233] The inventors have proposed to use a combination of members of the cholate family, such as deoxycholate and taurodeoxycholate permeation enhancers, and SNAC (sodium salcaprozate, sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) transport/permeation enhancer or non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) to bind to semaglutide to form a protective barrier to pH changes, to enhance solubility to minimise pepsin enzyme degradation of GLP-1 drugs in the stomach and enhance mucosal absorption at several points in oral-gastrointestinal tract. [00234] Both the cholates (see Figure 3) and SNAC (see Figure 4) are also surfactant- like, with carboxylate polar heads and non-polar tails. Semaglutide has numerous amine and arginine sites (five) that would be positively charged at pH<8, and capable of binding many negatively charged cholate and SNAC molecules, to form a protective coating that bristles with non-polar tails around each semaglutide molecule to prevent peptidolysis and pH change effects (peptide protection hypothesis). They may form individual molecular particles, or agglomerates. [00235] Dapagliflozin is an interesting molecule in that it is itself surfactant-like, with a polar headgroup sugar and a non-polar tail (Figure 5). It cannot bind ionically to the cholates (see Figure 3) or SNAC (see Figure 4), since there are no ionizable atoms, or to semaglutide. However, it potentially acts as a non-ionic surfactant and help to stabilize the semaglutide particles. The dapagliflozin may interleave with the cholate tails and stabilize them so that can point out into the water phase. [00236] When dapagliflozin, semaglutide, cholates and SNAC are combined in water and nanosized, in addition to phosphatidyl choline surfactant, semaglutide+cholate+SNAC ionically bonded nanoparticles will form, with outward-pointing non-polar tails stabilized with the non-ionic dapagliflozin “surfactant” (and dispersion aide phosphatidyl choline), a four in one particle combo (see Figure 6). These nanoparticles will have a particle size (by volume and number) below 2000nm. Dapagliflozin is poorly water soluble (1mg/mL) and this combination will provide greater solubility in water, and enhance mucosal absorption. [00237] The formulations are freeze dried and prepared in the form of a wafer for sublingual delivery. [00238] The present invention will now be described with reference to the following non- limiting Examples. The description of the Examples is in no way limiting on the preceding paragraphs of this specification, however is provided for exemplification of the methods and compositions of the invention. B EXAMPLE 2 – PREFERRED DOSES AND CONCENTRATION RANGES [00239] A formulation of the present invention, in the form of a solid dosage form (wafer), was prepared in accordance with the method and ingredients below and as set out below in Table 1. [00240] Wafers of the invention were prepared using the following methods. Sodium carboxymethylcellulose and sodium alginate were added in a portion of purified water by mixing thoroughly with a stirrer. The mixture was then heated to 50°C for ten minutes to allow dissolution of the polymers. Once the solution cooled down to room temperature, sodium glycodeoxycholate, sodium deoxycholate, carboxymethyl cellulose, sodium alginate, SNAC (salcaprozate sodium), soy lecithin lactose, mannitol, polyethylene glycol 2000, glycine, microcrystalline cellulose were added individually, under stirring to obtain a homogenously solution. This solution was then homogenized into nanoparticles. The viscosity of the solution and particle sizes were measured at 25° C using a Brookfield Digital Viscometer (Brookfield Engineering Laboratories Inc., MA, USA) and Malvern Laser PSD Mastersizer 2000 respectively. [00241] Wafers of the invention were freeze dried using the following methods. The resulting mixture was transferred by pipette and accurately weighed into pre-formed blister packs, and then transferred into a freezer (-30° C) for approximately 24 hours. After freezing, the sample was freeze-dried (DYNAVAC, Australia) for 24 hours using standard methods known in the art. The prepared sample was stored in desiccator over silica gel at a room temperature. [00242] Uniformity of Weight: The uniformity of the weight of the fast-dissolving dosage wafer form was tested in accordance with the British Pharmacopoeia (BP) 2009 test. Twenty wafers from each of the formulations listed in Table 1 + 2 were individually weighed, and the average weight and relative standard was calculated. All the prepared wafers from different formulations were within the accepted weight variation from between 0.25 to 2%. [00243] The strength of the fast-dissolving solid dosage wafer forms, i.e. their ability to be reduced from a solid substance into smaller pieces was measured. The test was conducted according to BP 2009 method (i.e. friability of uncoated tablets), using the Erweka friability tester (Germany). A sample of 20 wafers was weighed accurately and placed in the apparatus. A rotation time of four minutes at 25 rpm was used. Wafers were removed and reweighed and the percentage weight loss was calculated. It was found that the weight loss of the 20 wafers ranged from 8 to 20%. Although this weight loss does not comply with the BP 2009 standard of about 1 % weight loss for compressed tablets, there is no such standard for wafers in either the BP or USP monograph. [00244] Moisture Analysis: The moisture content of the wafers was analysed after lyophilisation using the 870 Karl Fisher Titrino Plus (Metrohm Ag, Germany). The results show that the residual moisture content varied between 1 % to 5% for different formulations. [00245] Various batches of the solid dosage wafer form were then prepared based on the formulation shown in Table 1 and Table 2 B.1 RESULTS [00246] Suitable compositions can be prepared according to TABLE 1 and TABLE 2. _{, , r} go_, e g E m mg dⁱ _t SS 4 ⁶ _. m an ON 1 ⁰⁰ _{. ;} e D^O _, _I g e3 d_, g_i ^s DT m ⁱ _t gm0_i ^{x l} EA 7 _l ^{u m 1} d RR _, g R ⁴en T g_; a_. 2da EN m ^ri 3g _{l, ,} ⁱ _{t ;} _l g FE m EC e1 _l ^yg^um emg RN dⁱ _t 2 POS _r v^{i 8} _{. l} ^{a 2} ue E ^CE _l ^ugo _t _, a1 n _, dd g_; ⁱ _{t )} R G a DN g _r gag mem em n ONA _l ^t mem M A R S51 ^A ₍ ² _. 151 x e02 r^C D ¹ _. w ⁽ %9%8%7%- d ⁱ 0000000 6⁵ _l ^ug o_{; ; ; ; ; ; ; ;} m_{; ; ; ; ; ;} g⁸ _. gggggg01113 n 0 oⁱ N _; % ta ^A %0^1; ₎ ^2; ₎ ^{3; 4 ;} ^; ₎ cnm1 _l ^sggggggg ammmmmmmm0mmmmm ; 49494m9_; g_; 1 g_; g r E 1¹ _{) )} ^w t S 0^; _/ ₎ ^w _/ ^w _/ ^w _/ ^w _/ w ⁽ _. ⁱ ^e _l ^d _; 5 g _l ^d1 13 25 37 49 51 73⁹ _. g1_; 2_; 4_; 5_; 7_; 8_; mmm 0 _r u . ^w _/ w ⁽ w ⁽ ww u om u_. 5 o0_. 0_. 0_. 0_. 0_. 0⁸ _. 00 ; m 7_. gggggg369 mmmmm 012 n O 0 ^{( (} %_i ^{g c 2 c} _{; ; ; ; ; ; ;} g038383m81_; 11 ec ^D _: w ⁽ %%%%5 ^f e eggggggg _; 124578g_; g_; g n D n 8765⁵- h so ^t sm t 0mmmmmmm4g_{; ; ; ; ; ;} E oⁱ % 9^1; ₎ ^2; ₎ ^3; ₎ ^{4; 4;} ca o dg o 246802 d¹ _. ² _. ³ _. ⁴ _. ⁵ _. ⁷ _. ⁸ _. ⁹ _. mggggggm2m5m8 o R a^; _{) ) )} e _l m _l ^e00000000⁶ _. mmmmmm012 c R ^r _t ^w E n^w _{/ /} ^w _/ ^w _/ ^w _/ ^w _{/ f} ^e1 _{; ; ; ; ; ;} 0272727111 w ^o b_; bgggggg_; g_; g_; 124578_{; ; ;} d F ew ⁽ w ⁽ w ⁽ w ⁽ w ⁽ a_i ^t g_. a_i ^t g_{; ; ; ; ; ;} ggg n E c ^{( s} _t umg um9m1 m3m5mmmm ggggggmmm a n %%7%6%5%4%5_i ⁿo 00m 7913m R o ^s 0 ^{s 0} _. ² _. ³ _. ⁴ _. ⁵ _. ⁶ _. ⁸ _. ⁹ _. ⁵ _. m1 m6m1 m6m1 m6147 P C 8123 46 p A 15 A 0000 00 00 012 45 78012 e 11 1 so d S d S e A r_r L _t e_f ^C R _i ^sn e_r ^O og P Y ^a ^{- L} _I ¹ ¹ M - P A L E F G L B A d T _; n ea d ] ⁱ _; _t e E _l ^udⁱ _t 7 M ga 42 A N a^ri N^O _{I . l} n , ex 0 0 _[ L Te _l ^ye_; ^. ₎ A Adⁱ _t evee dd C_I L U_l ^{u i} _t g aⁱ _t ⁱ _t _l a M Ma ⁿ _r ^ugn E R H m e_l ^ae i C Oe _l ^t F S ^a ₍ u^s d^xi _l _i ⁿz ,_l ^ofi iⁿg_l g zma l^{o 5}x fi_{l i} e . gⁿb az_, g mp_l ^of g i m 0m_l 1 eg0 , u0 iⁿz_l ^{y t} _r ² l e ^e vd_i ⁿz _; g_; g m2m 55 16 _; 1 g_; g m1 m 54 16 _; 1 g_;g m0m 53 16 _; 1 g_; g m9m 42 16 _; 1 g_; g m8m 41 16 _; 1 g_; g m7m 40 16 _; 1 g_; g m6m 49 15 _; 1 g_; g m5m 48 15 _; 1 g_; g m4m 47 15 _; 1 g_; g m3m 46 15 _{; ; ; ; ;} gggggm_; 1 g_; 1 g_; 1 g_; 1 g_; 1_; ^; ₎ w gg ⁽ w ⁽ w ⁽ w ⁽ w% ( 5 _l ^ucm o l^sggggg_;g_;g_;g⁴ _. m0mmmmm01_; 1_; 1_; 1_; 1_; 1_; 1_; m_. ^w _/ %%%%%³- n ⁱ 0 3^am7m9m1 m3m5m7m9m01505050 1 _; gggg g_; 245781_; gggm2m 45m8m1 m40g w ⁽ 10987^6; _{) l} ^do ^t _l ^du⁰ _. ¹ _. ³ _. ⁴ _. ⁵ _. ⁶ _. ⁷ _. ⁹ _. g_{; ; ; ; ;} gm2m5m8m1 m4m7m0156890 _; 1 g_; 1 g_; 1 g_; 1 g_; ¹ m5 ¹ go ^; ₎ ^2; ₎ ^2; ₎ ^3; ₎ ^4; u ) og o0_; 0_; 0_; 0_; 0_; 0_; 0_; 0m 3_. mggggg 9mmmmmm1235679 t² %1 ^w _/ o _: ^w _/ ^w _/ ^w _/ ^w _/ ^w _/ w ^{c m c} _; ( es1 egggggggg0_; smmmmmmmm_; g42934596491111111 89_; g_; g_; g_; g_; g_; g_; gm1 m 44m7m0m1 ^t nwwwww _; 3_; g o^{i ( ( ( ( (} % og o68024680gm_{; ; ; ; ; ;} m8ggggggm1 m4m7mmmm15 9g _t 5 ^{d d 0} _. ¹ _. ³ _. ⁴ _. ⁵ _. ⁶ _. ⁷ _. ⁹ _{. ;} mmmmmm 0369_; 161811 mm0 a^r _t %0%9%8%7%6⁴ _{- l} ^{e m} _l ^e0_; 0_; 000000² _.0g38383811213151617181g_; g_; g_; g_; g001_; n ^{1 1 2345} b0 a ⁵ b _{; ; ; ; ; ;} agggggggg_; m72_; 3_; 5_; 6_; 8_; 9_{; ;} g_; g_; g_{; ; ; ;} g e^; ₎ ^; ₎ ^; ₎ ^; ₎ ^; ₎ ^; _{) i} ^t o _i ^t mmmmmmmmg_; ggggm0mmmm ² c u ^t u57913579mgggggggmmmmmmm435669729o ^t m n 0 o^w _/ ^w _/ ^w _/ ^w _/ ^w _/ ^w _/ ^sg ^{s 0} _. ¹ _. ² _. ⁴ _. ⁵ _. ⁶ _. ⁷ _. ⁸ _. ¹ _. mm2m7m2mmm0369258 11 11 11 5 C^w ₍ ^w ₍ ^w ₍ ^w ₍ ^w ₍ ^w ₍ A m A 000000000623576287911213141617181 t _i ^snog a_t n a ²- TL G S ; _i ⁿz l^ofi_l gap m₎ _. e_i ⁿ iⁿ _, z_l ^yz l^o l ^f ^oe f vi_l i_l ⁱ _t g gau n_r ^t _r ape ^e a_l ^t d D^a ₍ n a ^s _t ^s ⁿ _t ^s _t ^s _t _i o _i ⁿo _i ⁿo _i ⁿ p o l p_l p p a a _la _la i^mc _i ^mc _i ^mc _i ^m e d e d e c d e d n o ^{2 2} _r _i _{i i} ² i ^{2 c} ⁿh ^{n n} _i ⁿ i h h h ^m ^t _i ^t _i ^t _i ^{t 2} ^{w w w w} _. 0 01_; g m0 ¹ o ^t 1_; g m5 ¹ o ^t 1_; g m5 ² o ^t 1_;g m0 ⁵ o ^t 1_; g m_. 0g 0 ¹ m5 o ^{t 2} 1 o _; ^t gg mm 00 01 ² _; g o ^t m0 1_; ⁵ go ^t mg ¹ m eo _i ^g _{. l} c pp ^t 01 ¹ _. ce _{; f} ¹- ^{f 1} _{- i} ^{g f} 0_; ^s _{t l} ^u g_; 0 c_; %a_l ^u _; B_. nGGGGG snsn ; ^d %1 ^o %hc %h _i ⁿ g 0 cg ⁱ c onm ¹ _i ^mnm ⁵ _. ^s _t ^{( ( ( ( ( a} _r ^a _rmg % ² _; ^s _t ⁵ _. 0a ⁵ _. % 0a 0p_l ⁱ -¹ _l _. m 1 _i ⁿ %_i ^{n d}0 c ⁱ 0 ⁷ n ¹ e ¹ e ¹ e ¹ e ¹ e ^t- ^t- o _; e_{f ;} e_f ¹- au ³ %5e d _l ^du ³ dn _. edⁱ dⁱ dⁱ dd oo05 ⁰ _. h_i ^{t 5} _. p % ^o% ^o%_i ^moo ^{t 0} _. oo ^t _. m_i ^m _t p_t p_t pⁱ _t pⁱ _{t ;} ^{c c} _; ⁷ 0 0_l 1 1 g 0 t _: c ^c 0^{2 c} d ^a n d pxee o n ^w a ^s _t ^s _t 2 d _: n _: n_i ⁿ _: n_i ⁿ _: nees_{; :} n_i ⁿ 2 e hes_; ⁱ _r ⁰ _. 0oeeeee 0b ^{p p p p p} _l ^ess pocom ¹0 on _i ^{m d}og _i ^t og ^{d 6}0 eeeee c 1 ⁱ oⁱ c oⁱ ooⁱ ooⁱ m oⁱ m m_l ^u _l ^uo ^t _{; t} a _t g a^r _{t ;} a^r _t e _t p _t p _t ^{2 d} ^d a^r _{t l} 0 _t ^{w d}m0 ez H ^{2 e} _i ^k a a^r _{t l} a a^r _{t i} ⁿ _l ^e a^r _t d_l ^e e ^p n d^l _{- i} ^kl _{- i} ^kl _{- i} ^kl _{- i} ^kl- oc ^{g g}gm n%0 n ² n n nh_i ^t b ³ o nnab ³ o ^e _r neah en r onononono₎ mmm0 e 10 c1 e_i e_i ^mc e_i ^mc e a_i ^{t t} e_; a_i ^{t t} % % ^f e ^t _r gggggm_i ^ud_i ^ud⁰ _. ¹ n_; c o nⁿ c oh_i ^t necec ^wug c ug 7 4 ^di o 0^o _t C% 9 C w C ^d no 2 C ^d nod ^s 2 Cn a A ^m no% ^s 1 C04 A ^m 1³ _. 0 ⁷ _{. l} o^w _t s ^e _f acacacacac_i ^uoo es ^e 0% 1 % 4% 1 S B e L _r P_l ^u g_l ^u g_l ^u g_l ^u g_l ^ud go s ^s a ^s a - o_r g - e_t ⁿ g i_l ^o _r ⁿi c ^e _{t l} ^y _r c aⁱl_i ^. _{t t} ny ny ^bne ¹ _{- r} n Ec e _r Ec e _{r .}e _. n _i ^v e -cg Pe i^{v i} _t Ls _l ^{d a} _r g a ^{a i}l n G_i b _t o^{f e} _t oⁱ _t ^; _r no ae ⁱ _t ^; _{r ;} s ce_; s ceno p i^. _r eoⁱ _, _t ^s _t ^a _t n _f a_r ac _i ⁿ i^s ecnc aecc ⁱ _t h l^yd ⁱ _t h a _l ^yd _t e a ac ^h _{- l} ^a n ^s u _i ^eeg _r ^Sd-^m _r aⁱ _t a^. _t e n naⁱ _t a^. _t e n oooo na ^o _r c_{i i} ^pdⁱ _t ^e _t _i ⁿ e_i ^xr _r e ehnpee^m _r ehpecucu cucu ^m _r eh ^e _t ^r nc c d _t xp _i ^s _i ⁿ a pu P e hg a Pn ee hg a M M M M Pn e E^e _r Ee p D B M S . e_{t . r} e_i ^d l^a _t c 0 e o _. es s e^a 00 s hcy ^e _{t l} ^o _{i i} ^c 2 _l ^o x _l ^{a u}l_l ^e _t ^co o o e an _l ^ul_l on o e e h c_{l .} e_t z oⁱ- a l^k ₎ c l^{y c} d cy y _r na^e _t ^g e oc x a po_{r l} ^a nⁱl l^y o ^h _t g e e _i ⁿ an d m _l ^g _l ^c _r o a y ^a s ^{o (} y _. e x n n _l e ;₎ ^e _t o _i ⁿ _l _l ^{e i} _tc ^a _{t i} ^z se k h_i ^t yes y^Sx m i^u m x i^u o m ⁽ i^u Cm_l ^aya c e e x_r e ^l _i ⁿ s ^h _t p _r e_l ^oc _l ^e _l _i ^e ^c p do d ^b o _r a d A_i ^uo c ^o _t o Nd_l ^{k e} _t yo _l ^y c _l ^yy^o _r om_i ^{c m} _r ^t o _r a mo S S C S So s as e S G a L P A M F H p P C ₎s⁽ _t neg ^a g ⁿi_lcyce ^rcⁱ _t ape ^h-^o _r ^e _t ne_-t _i ^snog ^a _t na_r ^o _t pec ^e _r) ²-TLG S ⁽ 2-_r e^t _r op s ss_i ^u _i ^t c p c ^s _; ^ass^ds s sa _i ^t cn n G GcGⁱ _t GaGⁱ _t GGxGG Gy c m G GcGⁱ _t G^e _t ^a n _r ^a _r ^a _r do ⁽ ce ⁽ e ^{l (} a ⁽ _l ^{c (} a ^{a ( (} _l ^{e ( ( (} xnn n n n o^a _r ^a _r ^{a a} _r ^a _r o^a _r o ⁽ ce ⁽ e ^{l (} a ⁽ s^t-o ^t- o^t- o ^{s 1} ^e _t e ^l d ^{- 1} l^t ed ^{– 1} p l^t ee ¹ a ¹ pe ^s _t n ^{1 1} p ^{1 1 1} _l ^{k t}- ^t _{- i} ^{c t}- ^t- c_{) r} ^t- ^{( 1 l} d^h- eds ⁽ ed^h- eededmeded edaoooo o^e _t o^e _t ed ^{- 1} l^t ed ^{– 1} p l e ^{1 e} ^t ed^h- ed_i ^c ^c e ^{c c}aⁱ _t aⁱ _t aⁱ _t ^o _r ⁱ _t Cⁱ _t ^o _{r i} ^mi _t ⁱ _t ocⁱ _t ⁱ _t ⁱ _{t r} ^{c c}na ^{c c} _l ^{a c} _l ^{a i} _t aⁱ _t aⁱ _t ^o _r ⁱ _t nos eseszpe ^spe ^spe^epeApe^e dpepe₎ pepe pe^e _t eses_l ^kes esyesype ^sp ^sp^epⁱ-oc oo^o _r ^el_i ^el_{i t} N _t o ^e _t s a x x ^el e^el e_t en_l p ^{p p p}n ^{p p}n b ^{p p p p p e}oo^u c _r o oooo ^p _i ^p _i ^pn ^po ^g _l ^uc l^uaeb l^c _i ^kl - eb t_i ^kl - ee t_i ^kl - eS t_i ^kl - ee t_i ^kl _-t mee_l ^aee e e_i ^kl _i ^kl yx_i ^k _i ^k _i ^k _i ^dc c_l ^uc l^uoc ( _l ^u c l^u _l ^kc a_l ^u _l ^k aeb r_i ^k - eb t_i ^k - ee t_i ^k - en t_i ^k _-tm_; ^{g g}a-_i ^uxmms ⁽ no_i ^s - nno_i ^s - nno_i ^s - nno_i ^s - nno_i ^sn d_{- -} o^l- ^l- enn _; ^l- ^{a g g e} _t ^g _; ^g _r ^g ^el _{- i} ^{s l} _{- i} ^{s l} _{- i} ^{s l} _{- i} ^sd_l ^e _i ^u _i ^uCgo ^r oo_l ^knonoxno_i ^cmm_l ^amxm^e _tsm_tsnonnonnonnonopdodoAacggo aacggo aacggo aacggo acg _r egga f acac_r gag_l ^ego_i ^u _i ^uy_i ^u _l ^e _i ^u cacpacnadodoxodopdo ^e _i ^ud ^ego o_i ^cacggo acggo a go cgacg ^sm ^{s s}N_l ^u _{t l} ^u _{t l} ^u _{t l} ^{u a} _{t l} ^{u a} _t ^e _{r l} ^u _l ^{u e} _{t l} ^u _l ^um_l ^u _l ^{k s s} _l ^sm ^s _i ^{d s}n_l ^a _{t l} ^a _{t l} ^a _{t l} ^a _t ao c a a S gn a gn a gn a gn a gn a P g gs e g go c g a a a^k a ao c ac a a _i ^ou gn a^u gn a^u gn a^u gn a

_; g_i ⁿ mz 5_l ^o ^{2 f}i_l _i ⁿg za₎ g l^on f am i_l c0 . g_, ² gag pm_i ⁿz m0m ⁵ _l ^o ¹ e_{, i} ^{n f}i_l _i g nz_l ^yz e_l ^of a i_l x _; g_; g m8m 51 17 _; 1 g_; g m7m 50 17 _; 1 g_; g m6m 59 16 _; 1 g_; g m5m 58 16 _; 1 g_;g m4m 57 16 _; 1 g_; g m3m 56 16 _; 1 g_; g m2m 55 16 _; 1 g_;g m1 m 54 16 _; 1 g_; g m0m 53 16 _; 1 g_; g ggg m _; w^w _/ 2109^w _/ m _. 2g c802468020_; mmmmm1 ggggggg_; gm9m2m5m8m1 g ⁽ w ^{( 2;} ₎ ^3; ₎ ^4; ₎ ^4; ₎ w _: m0 n ^{i 0} _. 0² _. 0³ _. 0⁴ _. 0⁵ _. 0⁶ _. ⁸ _. ⁹ _{. ;} g mmmmmmm g 739595814703m5416 _; 17 ; 18 ; 1⁰ _. m0 % ⁽ e ; 00 ²%^w ^; 2_/ ^w _/ ^w _/ ^w _/ d ³ o wwww% _l ^uo ^t _l ^s _; g_; g_; g_; g_; 0 g_; 0 g_; 0 g_; m2 gm1 _; 4 4_. 1 g_; 5 g_; 7 g_{; ;} 01345786 ² gg11111119 m_{; ; ; ; ; ; ;} 1 o ^tgggg_; ¹ ₎ ^{1 ( ( ( (} 5 c ammmmmmmm0_; mmmm0ggggggg_; 1m8mmmgo m ^{t w} _/ ^; ₎ ²- n ⁱ 2 w %%%% 414700 ⁷ _; g _l ^d7 0_. 9 1_. 1 3_. 3 4_. 5 5_. 7 6_. 9 7_. 1 9_{. ;} g62849 gm2457_; mmmmmmmg m_; g161718101 ^{( w} _/ 1098 w ^{233 4;} _{) l} ^du u m o00000000m0_{; ; ; ;} 1 ggggg407036925 11131415689m_; g_; g_; g_; 2_; g_; g % g 1 ^{( ;} ₎ ^; ₎ ^; ₎ ^; ₎ ^w ^ww _/ o0 ^c _{; ; ; ; ; ; ; ;} ³ _{. ;} mmmmm 11110 w ^{c 3} egggggggg0g517398_{; ; ; ; ; ; ; ;} ⁵m7mmm m0 _: % n1 _{/ /} ^w _/ ^w _/ e wwww ⁽ so ^t som6m8m0m2m4m6m8m0_; gm2_; 4_; 5_; 7_{; ;} gggggggg mmmmmmm o ^t40 16376m 899¹ oⁱ _t ^1; ₎ ^{( ( ( (} % o 5 ^dg d⁰ _. ¹ _. ³ _. ⁴ _. ⁵ _. ⁶ _. ⁷ _. ⁹ _. m9_; ggggg3692581 m1 mmmmm012456849_; _; 1 ; 1 ; 1 ; 1 o ; ^t a^r _t ^w _/ %0%9%8%7³ _{- l} ^{e m} 1 _l ^e00000000² _. g b_{; ; ; ; ; ; ; ;} 0m4062881 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 gggggg1_; nw ^{223 46} b_; agggggggg_; 82_; 4_; 5_; 7_{; ; ;} m g e ^{( ;} ₎ ^; ₎ ^; ₎ ^; ₎ ^; ₎ a_i ^t g _i ^t mmmmmmmmg_; gggggggg0mmmmm c ggggg n 4 ^wwww u ^m u57913579mg mmmmmmmm069258m o%_{/ / / /} ^w _/ ^s s 15171819151 C01 ^w ₍ ^w ₍ ^w ₍ ^w ₍ ^w ₍ A05 A⁰ _. 0¹ _. 0² _. 0⁴ _. 0⁵ _. 0⁶ _. 0⁷ _. 0⁸ _. 0¹ _. mmmmm25814703 ¹ 0m 732935517780111214151618191 ^o _t _t _i ^snog a_t n a ²- TL G S dn . n _, a_; _iz_l ^y l^oe_i ⁿz₎ f v i _l _l ⁱ _t ^o _i ⁿ ^fi z ga_l g_l ^o aⁿ _r a^fi_l pe a_l ^t pgu D^a ₍ m e^t _r e ^s _t ^s ⁿ _t ^s _t ^s _t _i o _i ⁿ p o _i ⁿo _i ⁿo _l p p p a _la _la _la _i ^mc _i ^m _i ^m _i ^m e ce c c ^{d d} e d e d n o ² _i ^{2 2 2} _r ⁿ _i ^c h _i ⁿ _i ⁿ _i ⁿ _i ^m ^t h_i ^t h_i ^t h_i ^{t 2} ^{w w w w} _. 0 ¹- w ^{( 1}- w ⁽ _; ^w _{/ ;} ^w _/ %am m e e5m %a5m e _{: ) ) ) ) )}% ⁵ _. ^e _r %^e _r %w ⁽ %w ^{( 5} _. 0_{f :} 5 ⁵ e ¹ _. e 0_{f :} 5 1^w _t ed¹- ¹- ¹- ¹- ¹-0u ⁵ _. _{; i} ^{g f} 0u 0 ;_i ^{g f 1}- ^e _r 0 u ¹- ^e _{r ;} ^odo i ^t _; ^oedo ^t e _l ^uPPPPP cLLLLL g u i^g %^s _t 0_{i l} ^ucg %^s _t _{i l} ^u B cg _. n ⁱ GGGGG%1 h _; c % a 1 h % ; ca ⁵ _. ^f % 0h ⁵ _. ^{f 1}- ⁿon 0ⁿ c 0h p_l ^{i m} 5 ¹- on p_l ^{i m 5} _. 5 ^{7 s} _t ^{( ( ( ( (} n ^{1 1 1 1 1} e e _; a _; c % _l ^d _; % _l ^d _; d eeeeee% _{. f} %_f a 5aug 5aug n _. ddddd⁵ 0 ^{o 5} _. %e%e o o _{. i} ^mi _t ⁱ _t ⁱ _t ⁱ _t ⁱ _t _: ^s _t 0 ^o 1 _f 1 _f ⁰ _. 0_i ^mc ^cm ⁰ 0 _. 0_i ^m m c ^cm d ^a n dpepepepepeno_i ⁿ _: ^s _t n_i ⁿ _: ^o n^s _{t :} ^o n^s _{t :} nees ³ _: ee0 e s ^{3 i} _r ⁰ _. 0o 0b ^{p p p p p} ⁱ _t o o ap ⁱ o oⁱ _i ⁿ oⁱ _i ⁿ o^{i d}oo n t o ^doo ^{t d 6}0meeeee^r _{t l t} p a a^r _{t l t} o_t o_t ^{2 d}2 ⁱ _t ^{2 d}2 ez H ^{2 e} _i ^k a a^r _t p a^r _t p a^r _{t i} ⁿ _l ^e _; a^r _{t i} ⁿ _l ^e _; e ^p n d^l _{- i} ^k n^l _{- i} ^k n^l _{- i} ^k n^l _{- i} ^kl-n _{l l} ec_i ^m n c e ne c_i ^m na na nh_i ^t b c e ag nh_i ^t bag ^e _r neah e e c_i ^r ooonono mec_i ^mec ^w _i ^t m e u0 c ^w _i ^t m u0 %7 % ^f e ^t _r g 4 ^di agagagagao no noc nc nd ^{s 3} nd ^{s 3} _l ^w _t ss ^e _f e C a A C a A 0 0 1 41 S B L _r ccccc C ^d 2 C ^d o o o 2 Ce d Ce d n ^o _t n ^o _t ³ _. ⁷ _. % %% oee P_l ^u g_l ^u g_l ^u g_l ^u g_l ^u g - o_r g - t ^o ^eni_{l r} g ni_l ^y _r a^. ncy ^e _t c ⁱl _{t t} c nyc _i bne ¹ _{- r} n E^e _r E^e _{r .} e _. e -cg Pe Ls _l ^{d a} _rn _i ^v _i ^{v i} _t a ^{a i}l n G_ib _t og f^e _toⁱ _t ^; _r no ae ⁱ _t ^; _{r ;} se_; sen po _, ^a _t n _f a _i ⁿ e cⁱ _t h c o ec d ⁱ _t h ⁱ _t ^. _r e eⁱ ^h _t _{- l} ^s ^a _t n ^{s a} _r g c _i ^s ncⁱ _t ^. _t aecncⁱ _t ^. _{t l} ^ya _l ^yda aecn ^ou _i ^ee^e _{t r} ^Sd-_r ^m _r aan eh ^m npeeg _r aan ococ ococ eh ^m _r npeeuu uu _r a eh ^e _t c_i ^r _i ^pdⁱ _{t i} ⁿ ed _i ^xr _t e nc cxp _i ^s p h a M M M M P e E E p D_i ⁿ a u P e h a P e g n ^e _r e B M S r _. ^e _t ^e _{t l} _t ^e ^e _t a- _l ^as o l^a _. znoyx ^e c oh _{. l}y ^e _t a ^o _{r i} ^d _l ^y p ⁿoc ^g en cy ^e _t ^h _{t i} ⁿ aa_l ^ka ^a _. e n ⁱl_l e x _l ^a e _l ^c _{r i} ^{c .} ₎ o o m_{. l} ^g e h ye ^a as ^o; _r ₎ ^e _i ⁿ n ⁱ _t _t on^e _t h _l ^e c ^a _ts _i ^z se l_i ^t ey e^y _r e ^Sxm _i ^ud mc xs m ⁽ sa^a c e s ^h _t p s _l ^e _l ^e o _i ^uyx o_l ^o _i ^u Cm i^{u e} _l ^ky e ax ^l _i ⁿc ^o _t e0_l ^oc o_{r l} ^o _i ^c pdoc l^y d ^b oo _r a^ul_l d A _i o Nd^cn_r o y _l ^y c _l ^y0y_i ^{c u}l_l ^m _r ^t _r mo g Se d C c S S s _l ^k o o m a S G L P 2 A M c o a S e o _i ^oo ₍ a 0 e F H p P C _;x _l ^ep mo ^c _i ⁿh_i ^tce ^{l -} _l ^t a ^s ^el_i b_-t _i ^snog ^a _t na_r ^o _t pec ^e _r) ²-TLG S ⁽ 2-_r e-_r ^t _r e -_r e-_r e-_r p o e_; - x_{) r} -_r -_r ^{- -} ¹ ₎ o^t _r o ^t _r o^t _r o^t _r o_l ^e- ¹- a₎ _l ^{c 1}- s⁽ _{t )} 1- oc₎ 1 s⁽ _t c_{) ) ) ) )} n^{1 1 1 1 1} c₎ ee^e _t e_r e _r e_i ^dc₎ 1 ₎ ^e ¹ _ts₎ 1 s⁽ _{t )} 1 _l ^ka pP PaPneP_{) -} Pne ⁱ _{- - - - -} ^t _r ^t _{r l} ^{a t} _r ^t _r ^t _{r - -} oPP PPP^e _t ooyoo o ^aP P ^e- Pn- P_rpp ppp L_; LsLgLmLg LL LLL_l ppxpp p_i ^cL L_i ^cLeLoss sssmGxG ⁽ G G_i ^uG _l ^sGG GGG^ayssoss_; soG_;x n g ⁽n ^an nnno _r ^a _r ^a _r ^a _r ^a _r c ⁽ _l ^{e (} C A ^{( a} g ⁽ do ^{( a} g ^{a ( ( ( ( (} xnn_l ^knnxnn GoG ^aG o^{a a}a^{a a} _l ^eaa ⁽ _l ^{e ( i}- ⁽ g ^{( e} _t ^t-o^t- ^t- ^t- ^t _{- )} ¹ p e ¹ eN ¹ eⁿi_l ¹ e ^{s 1} eⁿi_l ^s _t n ¹ e ¹ e ¹ e ^{1 1} _l ^k _r ^t _{- r} ^t _{- r r} ^t _{- r} ^t- p_r ^t _{- l} ^{k 1} p ¹ no ^{1 n}i_l ¹ _l ^ay ^co ooom e ^c se_; ^{c c c} _i ^udm i_t odⁱ _t ^Sdⁱ cyd^{i e} _t dⁱ cy edⁱ dⁱ _;xdee i dⁱ dⁱ a_r oo^e _tsoomooa_r edme i od^{i n}edⁱ ce ydⁱ xo sxesesesdop ^c e_i ⁿp - _t e_i ⁿpc_t a_t eepezpc ee _i ^m _t dp_t ep_l ^e _t epp_t ep_t epe^e _t ^c e ^c ses ^{e c} e ^c sec s₎ ^c eo s ⁽ _t p ^c _t e_i ⁿp - _t e_i ⁿpc_t eepe_l ^kaoco ^uc_l ^epocococ ^{s p}h_i ^{t p}h_i ^{t p r}c^{i p o} _r p ^{p r}c ob ^{p p}m s o ^{p p p e}oco_i ^d ccococ^e _t oc^e _t ^ph_i ^{t p}h_i ^{t p r}c ^p _r _l ^e _t ecece_t eaeⁱ _t meeceee ^g _l ^u ^gmo_l ^u _l ^u _l ^ua_i ^k _i ^{d a} _l ^a _l ^aececeⁱ _t e^e _tm c ^{g g g}z^l e_i ^ke ^l _i ^kap_i ^k _l ^c _i ^kap ^e _i ^k _i ^k _{) i} ^k _i ^k _i ^kc_l ^u _l ^u _i ^c _l ^u _l ^uyx_l ^uyx_i ^ke_i ^ke ^l _i ^kap_i ^ks_i ^o- n ^{l - l}- n ^{– l}- ne^l- na^l s- ne d^l- n^l- n^e _t ^l- n^l- n^l- n ^{a g g}o ^{g g}o ^go^l- n ^{l - l}- n ^{– l}- ne^l- n ^e ^um_{) i} _i ^c ^u m i^um i^um_r _i ^upo_l ^t o_l ^t o^h- o ⁽ o^h- e^r oo_l ^aooo_i ^cm i^umn i^uam i^um i^u _l ^km i_l ^ko_l ^t o_l ^t o^h- ondodm i^udddagaa sgaa sga^o _r gaCga^o _{r r} egg f aayxgagagaondd_l ^k a add_r ^uda_r gaa sgaa sga^o _r gaoⁱ- ^so sdo so so s _l ^cac l ^el_i c l ^el_i c l ^e _t c l Ac N_l ^e _t ^e _r c l c l o l c l ccao so s _r o so s^e _t o s^e _t c^el c^el c^e _t cn a ao s a a a^s ₍ ^u g b^u g b^u gn e^u g S^u gn e P^u g^u g^k a^u g_l ^u g_l ^u g_l ^k a a a^o ₍ a as e as e_l ^u g_i b_l ^u g_i b_l ^u gn e_l ^u go n _-t _i ^sn_.oxg_l ^e ^a _t pnmao_r c^o _{t )}p^e _tec_l ^ay^e _r x₎ o² _{- l} ^kaT_rL G^e _tsS ^{( e}2_i ^d-_r ce ^a ^t _{r i} ^coopnsan^a _l _r ^k ^t a_{- r}oo ^{c (}e^e _tso_l ^acy_l ^uxo ^g _l ^kma_i ^u _rd^e _tos ^{s e}a_i- ^cn_t o_i ^{s i}-nnoogna-_{) )} ¹- s⁽ _tPnLeGg ^{( a} ¹ geⁿi_ldⁱ _t cypcee ^{p r}ec_i ⁱ ^k _t ^l- apneog^h-a^oc_r _l ^{u e} _t gn e [00249] Another preferred proposed formula sublingual semaglutide with dapagliflozin (per wafer) is also presented in TABLE 3 and TABLE 4. TABLE 3: One preferred proposed formula sublingual semaglutide with dapagliflozin (per wafer): Ingredients Quantity D S S S S C S S W TABLE 4: Another preferred proposed formula sublingual semaglutide with dapagliflozin (per tablet or capsule): I y D S S S p C C S M g g [00250] A schematic diagram of the process of semaglutide/dapagliflozin delivery via the gastrointestinal track is presented in Figure 7. C EXAMPLE 3 – SINGLE DOSE PHARMACOKINETIC STUDY OF LIRAGLUTIDE FOLLOWING SUBLINGUAL, INTRAVENOUS AND SUBCUTANEOUS ROUTE OF ADMINISTRATION IN MALE SPRAGUE DAWLEY RAT. [00251] STUDY AIM [00252] To determine the pharmacokinetics of liraglutide following sublingual (formulations of the invention), intravenous and subcutaneous route of administration in male Sprague Dawley Rat. [00253] MATERIALS [00254] TABLE 5: Liraglutide wafer formulation A T t it Li l tid f f l ti A [00255] TABLE 6: Liraglutide wafer formulation B [00256] Test System [00257] Species: Rat. Strain: Sprague Dawley. Sex: Male; Rationale: Sprague Dawley rat is commonly used rodent species in the pharmacokinetic evaluation of drugs and acceptable to the regulatory authorities; Source of animals: Hylasco Biotechnology (India) Pvt. Ltd., Hyderabad; Total number of animals: 24 Rats (6 rats/group); Age/ Body Weight at study initiation: 7-10 weeks, 250-350 g; Veterinary Examination: Prior to the final assignment to the study, animals will be subjected to complete veterinary health examination to ensure that the selected animals are in a good state of health; Animal Identification: Animals will be uniquely identified by individual tail marking with a permanent marker along with cage card. [00258] Acclimatization: On receipt from supplier, the animals will be examined for any external signs of ill health and aberrant behavior prior to acceptance. After health examination, animals will be quarantined for one week under test conditions and then acclimatized for a minimum of 5 days in study room. Only animals without any visible signs of illness will be used for the study. [00259] Animal catheterization: Under Ketamine and Xylazine anesthesia, all animals will be cannulated in right external jugular vein. Rats will be surgically implanted with a catheter (jugular vein, Polyethylene-50 tubing attached to Polyurethane-40 catheter) for blood collection. Rats will be allowed to recover for minimum of 48 h after cannulation, before inclusion in study and drug administration. General animal health and cannula patency will be confirmed prior to dose administration. [00260] METHODS [00261] Husbandry [00262] Housing Conditions: Standard laboratory conditions, temperature will be maintained between 22±3°C and relative humidity between 30–70 % under a 12 h light/dark cycle. Air changes of 12-15 times per hour via a centrally placed air intake and peripheral ventilators will be maintained. [00263] Accommodation: Each animal will be placed in individual polycarbonate cage with stainless steel grill top with facilities for feed and water bottle and bedding of clean corn cob. [00264] Feed: Hypro pelleted rodent feed manufactured by Krishna valley Agrotech LLP, Sangli, Maharashtra (India) diet source, was provided ad libitum. Sublingual group rats will be fasted overnight. No feed will be provided. Subcutaneous and IV group rats will be free access to feed. [00265] Water: Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd., Mumbai - 400001, India., will be provided ad libitum in polycarbonate bottles with stainless steel sipper tubes. All rats will have access to water ad libitum. [00266] Animal handling: Experiment will be carried out by qualified & trained scientific personnel (trained in animal handling, drug administration and experimentation). [00267] Body weight: On the day of dosing. [00268] Clinical signs: Animals will be observed for any apparent clinical signs of ill- health and toxicity during study duration. [00269] Dose Formulation Preparation [00270] The dose formulation will be prepared freshly on the day of dosing. [00271] TABLE 7: Group Allocation and Treatment G (Dose) Liraglutide wafer 1 2 3 4 [00272] Note: Permanent IDs of Rat used in this study will be captured in the final report. [00273] TABLE 8: Formulations G 1 2 d e 3 m d e 4 m [00274] TABLE 9: Formulations A and B # 1 2 3 4 5 6 7 Glycine 4.4 4.4 8 9 1 1 1 1 1 [00275] The range values for selecting values for Formulation A and B above include: [00276] Liraglutide - 2.5mg to 50 mg per wafer, including: 2.4mg; 2.5mg; 2.6mg; 2.7mg; 2.8mg; 2.9mg; 3.0mg; 3.1mg; 3.2mg; 3.3mg; 3.4mg; 3.5mg; 3.6mg; 3.7mg; 3.8mg; 3.9mg; 4.0mg; 4.1mg; 4.2mg; 4.3mg; 4.4mg; 4.5mg; 4.6mg; 4.7mg; 4.8mg; 4.9mg; 5.0mg; 5.1mg; 5.2mg; 5.3mg; 5.4mg; 5.5mg; 5.6mg; 5.7mg; 5.8mg; 5.9mg; 6.0mg; 6.1mg; 6.2mg; 6.3mg; 6.4mg; 6.5mg; 6.6mg; 6.7mg; 6.8mg; 6.9mg; 7.0mg; 7.1mg; 7.2mg; 7.3mg; 7.4mg; 7.5mg; 7.6mg; 7.7mg; 7.8mg; 7.9mg; 8.0mg; 8.1mg; 8.2mg; 8.3mg; 8.4mg; 8.5mg; 8.6mg; 8.7mg; 8.8mg; 8.9mg; 9.0mg; 9.1mg; 9.2mg; 9.3mg; 9.4mg; 9.5mg; 9.6mg; 9.7mg; 9.8mg; 9.9mg; 10.0mg; 10.1mg; 10.2mg; 10.3mg; 10.4mg; 10.5mg; 10.6mg; 10.7mg; 10.8mg; 10.9mg; 11.0mg; 11.1mg; 11.2mg; 11.3mg; 11.4mg; 11.5mg; 11.6mg; 11.7mg; 11.8mg; 11.9mg; 12.0mg; 12.1mg; 12.2mg; 12.3mg; 12.4mg; 12.5mg; 12.6mg; 12.7mg; 12.8mg; 12.9mg; 13.0mg; 13.1mg; 13.2mg; 13.3mg; 13.4mg; 13.5mg; 13.6mg; 13.7mg; 13.8mg; 13.9mg; 14.0mg; 14.1mg; 14.2mg; 14.3mg; 14.4mg; 14.5mg; 14.6mg; 14.7mg; 14.8mg; 14.9mg; 15.0mg; 15.1mg; 15.2mg; 15.3mg; 15.4mg; 15.5mg; 15.6mg; 15.7mg; 15.8mg; 15.9mg; 16.0mg; 16.1mg; 16.2mg; 16.3mg; 16.4mg; 16.5mg; 16.6mg; 16.7mg; 16.8mg; 16.9mg; 17.0mg; 17.1mg; 17.2mg; 17.3mg; 17.4mg; 17.5mg; 17.6mg; 17.7mg; 17.8mg; 17.9mg; 18.0mg; 18.1mg; 18.2mg; 18.3mg; 18.4mg; 18.5mg; 18.6mg; 18.7mg; 18.8mg; 18.9mg; 19.0mg; 19.1mg; 19.2mg; 19.3mg; 19.4mg; 19.5mg; 19.6mg; 19.7mg; 19.8mg; 19.9mg; 20.0mg; 20.1mg; 20.2mg; 20.3mg; 20.4mg; 20.5mg; 20.6mg; 20.7mg; 20.8mg; 20.9mg; 21.0mg; 21.1mg; 21.2mg; 21.3mg; 21.4mg; 21.5mg; 21.6mg; 21.7mg; 21.8mg; 21.9mg; 22.0mg; 22.1mg; 22.2mg; 22.3mg; 22.4mg; 22.5mg; 22.6mg; 22.7mg; 22.8mg; 22.9mg; 23.0mg; 23.1mg; 23.2mg; 23.3mg; 23.4mg; 23.5mg; 23.6mg; 23.7mg; 23.8mg; 23.9mg; 24.0mg; 24.1mg; 24.2mg; 24.3mg; 24.4mg; 24.5mg; 24.6mg; 24.7mg; 24.8mg; 24.9mg; 25.0mg; 25.1mg; 25.2mg; 25.3mg; 25.4mg; 25.5mg; 25.6mg; 25.7mg; 25.8mg; 25.9mg; 26.0mg; 26.1mg; 26.2mg; 26.3mg; 26.4mg; 26.5mg; 26.6mg; 26.7mg; 26.8mg; 26.9mg; 27.0mg; 27.1mg; 27.2mg; 27.3mg; 27.4mg; 27.5mg; 27.6mg; 27.7mg; 27.8mg; 27.9mg; 28.0mg; 28.1mg; 28.2mg; 28.3mg; 28.4mg; 28.5mg; 28.6mg; 28.7mg; 28.8mg; 28.9mg; 29.0mg; 29.1mg; 29.2mg; 29.3mg; 29.4mg; 29.5mg; 29.6mg; 29.7mg; 29.8mg; 29.9mg; 30.0mg; 30.1mg; 30.2mg; 30.3mg; 30.4mg; 30.5mg; 30.6mg; 30.7mg; 30.8mg; 30.9mg; 31.0mg; 31.1mg; 31.2mg; 31.3mg; 31.4mg; 31.5mg; 31.6mg; 31.7mg; 31.8mg; 31.9mg; 32.0mg; 32.1mg; 32.2mg; 32.3mg; 32.4mg; 32.5mg; 32.6mg; 32.7mg; 32.8mg; 32.9mg; 33.0mg; 33.1mg; 33.2mg; 33.3mg; 33.4mg; 33.5mg; 33.6mg; 33.7mg; 33.8mg; 33.9mg; 34.0mg; 34.1mg; 34.2mg; 34.3mg; 34.4mg; 34.5mg; 34.6mg; 34.7mg; 34.8mg; 34.9mg; 35.0mg; 35.1mg; 35.2mg; 35.3mg; 35.4mg; 35.5mg; 35.6mg; 35.7mg; 35.8mg; 35.9mg; 36.0mg; 36.1mg; 36.2mg; 36.3mg; 36.4mg; 36.5mg; 36.6mg; 36.7mg; 36.8mg; 36.9mg; 37.0mg; 37.1mg; 37.2mg; 37.3mg; 37.4mg; 37.5mg; 37.6mg; 37.7mg; 37.8mg; 37.9mg; 38.0mg; 38.1mg; 38.2mg; 38.3mg; 38.4mg; 38.5mg; 38.6mg; 38.7mg; 38.8mg; 38.9mg; 39.0mg; 39.1mg; 39.2mg; 39.3mg; 39.4mg; 39.5mg; 39.6mg; 39.7mg; 39.8mg; 39.9mg; 40.0mg; 40.1mg; 40.2mg; 40.3mg; 40.4mg; 40.5mg; 40.6mg; 40.7mg; 40.8mg; 40.9mg; 41.0mg; 41.1mg; 41.2mg; 41.3mg; 41.4mg; 41.5mg; 41.6mg; 41.7mg; 41.8mg; 41.9mg; 42.0mg; 42.1mg; 42.2mg; 42.3mg; 42.4mg; 42.5mg; 42.6mg; 42.7mg; 42.8mg; 42.9mg; 43.0mg; 43.1mg; 43.2mg; 43.3mg; 43.4mg; 43.5mg; 43.6mg; 43.7mg; 43.8mg; 43.9mg; 44.0mg; 44.1mg; 44.2mg; 44.3mg; 44.4mg; 44.5mg; 44.6mg; 44.7mg; 44.8mg; 44.9mg; 45.0mg; 45.1mg; 45.2mg; 45.3mg; 45.4mg; 45.5mg; 45.6mg; 45.7mg; 45.8mg; 45.9mg; 46.0mg; 46.1mg; 46.2mg; 46.3mg; 46.4mg; 46.5mg; 46.6mg; 46.7mg; 46.8mg; 46.9mg; 47.0mg; 47.1mg; 47.2mg; 47.3mg; 47.4mg; 47.5mg; 47.6mg; 47.7mg; 47.8mg; 47.9mg; 48.0mg; 48.1mg; 48.2mg; 48.3mg; 48.4mg; 48.5mg; 48.6mg; 48.7mg; 48.8mg; 48.9mg; 49.0mg; 49.1mg; 49.2mg; 49.3mg; 49.4mg; 49.5mg; 49.6mg; 49.7mg; 49.8mg; 49.9mg; 50.0mg. [00277] TPGS (d-α-tocopheryl polyethylene glycol succinate) penetrant/surfactant 0.1% to 20%, including: 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; 0.6%; 0.7%; 0.8%; 0.9%; 1.0%; 1.1%; 1.2%; 1.3%; 1.4%; 1.5%; 1.6%; 1.7%; 1.8%; 1.9%; 2.0%; 2.1%; 2.2%; 2.3%; 2.4%; 2.5%; 2.6%; 2.7%; 2.8%; 2.9%; 3.0%; 3.1%; 3.2%; 3.3%; 3.4%; 3.5%; 3.6%; 3.7%; 3.8%; 3.9%; 4.0%; 4.1%; 4.2%; 4.3%; 4.4%; 4.5%; 4.6%; 4.7%; 4.8%; 4.9%; 5.0%; 5.1%; 5.2%; 5.3%; 5.4%; 5.5%; 5.6%; 5.7%; 5.8%; 5.9%; 6.0%; 6.1%; 6.2%; 6.3%; 6.4%; 6.5%; 6.6%; 6.7%; 6.8%; 6.9%; 7.0%; 7.1%; 7.2%; 7.3%; 7.4%; 7.5%; 7.6%; 7.7%; 7.8%; 7.9%; 8.0%; 8.1%; 8.2%; 8.3%; 8.4%; 8.5%; 8.6%; 8.7%; 8.8%; 8.9%; 9.0%; 9.1%; 9.2%; 9.3%; 9.4%; 9.5%; 9.6%; 9.7%; 9.8%; 9.9%; 10.0%; 10.1%; 10.2%; 10.3%; 10.4%; 10.5%; 10.6%; 10.7%; 10.8%; 10.9%; 11.0%; 11.1%; 11.2%; 11.3%; 11.4%; 11.5%; 11.6%; 11.7%; 11.8%; 11.9%; 12.0%; 12.1%; 12.2%; 12.3%; 12.4%; 12.5%; 12.6%; 12.7%; 12.8%; 12.9%; 13.0%; 13.1%; 13.2%; 13.3%; 13.4%; 13.5%; 13.6%; 13.7%; 13.8%; 13.9%; 14.0%; 14.1%; 14.2%; 14.3%; 14.4%; 14.5%; 14.6%; 14.7%; 14.8%; 14.9%; 15.0%; 15.1%; 15.2%; 15.3%; 15.4%; 15.5%; 15.6%; 15.7%; 15.8%; 15.9%; 16.0%; 16.1%; 16.2%; 16.3%; 16.4%; 16.5%; 16.6%; 16.7%; 16.8%; 16.9%; 17.0%; 17.1%; 17.2%; 17.3%; 17.4%; 17.5%; 17.6%; 17.7%; 17.8%; 17.9%; 18.0%; 18.1%; 18.2%; 18.3%; 18.4%; 18.5%; 18.6%; 18.7%; 18.8%; 18.9%; 19.0%; 19.1%; 19.2%; 19.3%; 19.4%; 19.5%; 19.6%; 19.7%; 19.8%; 19.9%; and 20.0%. [00278] Sodium deoxycholate - 0.1% to 20%, including: 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; 0.6%; 0.7%; 0.8%; 0.9%; 1.0%; 1.1%; 1.2%; 1.3%; 1.4%; 1.5%; 1.6%; 1.7%; 1.8%; 1.9%; 2.0%; 2.1%; 2.2%; 2.3%; 2.4%; 2.5%; 2.6%; 2.7%; 2.8%; 2.9%; 3.0%; 3.1%; 3.2%; 3.3%; 3.4%; 3.5%; 3.6%; 3.7%; 3.8%; 3.9%; 4.0%; 4.1%; 4.2%; 4.3%; 4.4%; 4.5%; 4.6%; 4.7%; 4.8%; 4.9%; 5.0%; 5.1%; 5.2%; 5.3%; 5.4%; 5.5%; 5.6%; 5.7%; 5.8%; 5.9%; 6.0%; 6.1%; 6.2%; 6.3%; 6.4%; 6.5%; 6.6%; 6.7%; 6.8%; 6.9%; 7.0%; 7.1%; 7.2%; 7.3%; 7.4%; 7.5%; 7.6%; 7.7%; 7.8%; 7.9%; 8.0%; 8.1%; 8.2%; 8.3%; 8.4%; 8.5%; 8.6%; 8.7%; 8.8%; 8.9%; 9.0%; 9.1%; 9.2%; 9.3%; 9.4%; 9.5%; 9.6%; 9.7%; 9.8%; 9.9%; 10.0%; 10.1%; 10.2%; 10.3%; 10.4%; 10.5%; 10.6%; 10.7%; 10.8%; 10.9%; 11.0%; 11.1%; 11.2%; 11.3%; 11.4%; 11.5%; 11.6%; 11.7%; 11.8%; 11.9%; 12.0%; 12.1%; 12.2%; 12.3%; 12.4%; 12.5%; 12.6%; 12.7%; 12.8%; 12.9%; 13.0%; 13.1%; 13.2%; 13.3%; 13.4%; 13.5%; 13.6%; 13.7%; 13.8%; 13.9%; 14.0%; 14.1%; 14.2%; 14.3%; 14.4%; 14.5%; 14.6%; 14.7%; 14.8%; 14.9%; 15.0%; 15.1%; 15.2%; 15.3%; 15.4%; 15.5%; 15.6%; 15.7%; 15.8%; 15.9%; 16.0%; 16.1%; 16.2%; 16.3%; 16.4%; 16.5%; 16.6%; 16.7%; 16.8%; 16.9%; 17.0%; 17.1%; 17.2%; 17.3%; 17.4%; 17.5%; 17.6%; 17.7%; 17.8%; 17.9%; 18.0%; 18.1%; 18.2%; 18.3%; 18.4%; 18.5%; 18.6%; 18.7%; 18.8%; 18.9%; 19.0%; 19.1%; 19.2%; 19.3%; 19.4%; 19.5%; 19.6%; 19.7%; 19.8%; 19.9%; and 20.0%. [00279] Dose administration [00280] Group 1 & 2 Rat, wafer will be placed in moist sublingual cavity. Wafers will be crushed and weighed on an accurate balance and placed in the sublingual space under isoflurane anesthesia for 4-5 min followed by up to 1-2 drops of water to assist in disintegration (use minimal amount required to disintegrate wafers). [00281] Note: The sublingual mucosa moistness will be ensured prior to administering the SL wafer by administering a small quantity of water into the SL space, just prior to anesthesia. [00282] Group 3 rats will be administered subcutaneously on the dorsal side towards Cranial. [00283] Group 4 rats will be administered intravenously through lateral tail vein. [00284] Blood Collection and storage of samples. [00285] Site of blood collection: Jugular vein via cannulation. [00286] Anticoagulant: K₂EDTA (20 µL of 200 mM solution per 1 mL of blood). [00287] Blood collection time points: 0 (pre-dose), 0.083 h, 0.25 h, 0.5 h, 1 h, 2 h, 4h, 8 h and 24 h post dose (Total 9 time points/rat). [00288] Volume of blood collected: ~0.2 mL at each time points from each rat. [00289] Blood sampling procedure: Serial sampling. [00290] Blood centrifugation time: 4000 rpm for 10 minutes at 4 °C. [00291] Matrix: Plasma. [00292] Matrix storage: -70 ± 10 °C until analysis. [00293] Matrix labelling details: Study number, Group, Animal ID, and Time point. [00294] Note: Blood samples will be kept on wet ice until centrifugation. Centrifugation will be done within 30 minutes of collection and plasma will be checked for hemolysis. If samples are hemolyzed, another sample will be taken as soon as possible. Prepared dose formulation will be discarded after the completion of in-life phase. On completion of the last blood sampling, animals will be sacrificed, and carcasses discarded. [00295] Bioanalysis [00296] Matrix: Plasma. [00297] Analyte: Liraglutide. [00298] Bioanalysis will be performed by fit-for-purpose analytical method using LC- MS/MS. [00299] Upon finalization of study report, remaining biological study samples will be discarded. [00300] Pharmacokinetic data analysis and evaluation [00301] Pharmacokinetic Software: Phoenix^® Software, version 8.3, USA. [00302] Pharmacokinetic Parameters: C0, Cmax, Tmax, AUC0-t, AUC0-∞, Kel, T1/2, Vd, Vd,/F, Cl, Cl/F and MRT_last. [00303] RESULTS [00304] The study is to determine the relative bioavailability of two formulations of a sublingual lyophilised liraglutide wafer compared to subcutaneous injection of liraglutide (Victoza) in rats. We expect the relative bioavailability to be in the range of 2-50%. In addition, we expect to see more rapid absorption into plasma following administration with the sublingual wafer compared to subcutaneous injection. [00305] DISCUSSION [00306] These results would represent to our knowledge the first data available on the relative bioavailability of sublingual administration of liraglutide. Obtaining systemic absorption of liraglutide via sublingual administration with this novel wafer creates the potential for a non-injectable formulation of liraglutide. At present, liraglutide is only available as an injectable product. Such a product would be non-invasive, easier to use, convenient and improve patient compliance. D EXAMPLE 4 – SINGLE DOSE PHARMACOKINETIC STUDY OF SEMAGLUTIDE FOLLOWING ORAL AND SUBLINGUAL ROUTE OF ADMINISTRATION IN MALE C57BL/6 MICE. [00307] STUDY AIM [00308] The goal of this study was to determine the pharmacokinetics of semaglutide following oral and sublingual route of administration in male C57BL/6 mice. [00309] MATERIALS AND METHODS [00310] This study was performed in overnight fasted male C57BL/6 mice. Rybelsus^® Sematglutide, 14 mg Tablets (Batch No.: PS6LE23) and Semaglutide B-14 mg Freeze-dried oral disintegrating Tablets (wafers) (Batch No.: B240836), were test items used in this study. Dose formulations were prepared freshly on the day of dosing. 0.5% of methyl cellulose in Milli Q water were used as the vehicle. See Tables 33 to 35 for further information on the formulations. [00311] TABLE 10: Group allocation and treatment l [00312] Note: Permanent Id’s of mice used in this study were Mj1824 to Mj1841 [00313] Blood samples were collected through retro orbital sinus puncture at 0 (pre- dose), 5 mins, 15 mins, 30 mins, 45 mins, 60 mins, 90 mins, 120 mins, 240 mins and 480 mins post dose (Total 10 time point) At each time points, ~0.2 mL of blood was withdrawn and transferred into pre-labeled microcentrifuge tubes containing 20 µL per mL of blood of 200 mM K2EDTA solution as anticoagulant. Blood samples were kept on wet ice and were centrifuged immediately at 4000 rpm for 10 min at 4 °C. Plasma was separated after centrifugation. Plasma samples were transferred into pre-labeled (Animal ID No., Time point, Study No., Matrix and Group) tubes. All plasma samples were stored at -70 ± 10 °C until bioanalysis. [00314] Bioanalysis was performed using fit-for-purpose LC-MS/MS method for the quantification of Semaglutide in plasma samples. [00315] The plasma pharmacokinetic parameters of semaglutide were determined from mean concentration time curves obtained following a single oral and sublingual route of administration in male C57BL/6 mice. Values are expressed as Mean ± SD and n=3 mice/time point/group. [00316] Plasma pharmacokinetic parameters were calculated using standard non- compartmental analysis (Phoenix^® software, version 8.3, Certara Corporation, Mountain View, California 94040/USA) using linear trapezoidal method with linear interpolation. [00317] RESULTS AND DISCUSSION [00318] No clinical signs, mortality or morbidity was observed in treated group animals at the doses tested. [00319] The plasma pharmacokinetic parameters semaglutide were determined from mean concentration time curves obtained following a single oral and sublingual route of administration in male C57BL/6 mice. Values are expressed as Mean ± SD and n=3 mice/time point/group [00320] In Group 1 (semaglutide tablet 10 mg/kg, oral ROA to Male C57BL/6 mice), time to reach peak plasma concentration (Tmax) of mean was 45 min and peak plasma concentration (Cmax) of 54.4 ng/mL. The mean exposure, AUClast was found to be 72 ng*h/mL. [00321] In Group 2 (semaglutide wafer 10 mg/kg, sublingual ROA to Male C57BL/6 mice), time to reach peak plasma concentration (Tmax) of mean was 30 min and peak plasma concentration (Cmax) of 720 ng/mL. The mean exposure, AUClast was found to be 794 ng*h/mL. [00322] TABLE 11: Arithmetic Mean plasma pharmacokinetic parameters of Semaglutide following single oral and sublingual route of administration to male C57BL/6 mice. M _last ( ) . . [00323] Note: NC: Not Calculated due to insufficient elimination phase; *: represents value should not be considered as %AUCexp >30%. [00324] TABLE 12: Arithmetic Mean plasma concentration time profile of Semaglutide following single Oral and Sublingual route of administration to male C57BL/6 mice. Group 1: Group 2: [00325] TABLE 13: Individual plasma concentrations of Semaglutide tablet following single Oral route of administration to male C57BL/6 mice (G1: 10 mg/kg) 1 Mean 0 31.9 10.4 33.8 54.4 11.6 19.8 6.67 1.02 9.1 SD 0 14.9 13.1 33.3 57.2 10.2 19.9 11.5 1.76 15.8 [00326] TABLE 14: Individual plasma concentrations of Semaglutide following single Sublingual wafer route of administration to male C57BL/6 mice (G2: 10 mg/kg) Gr Tr tm nt Time Plasma Concentrations (ng/mL) E EXAMPLE 5 – SINGLE DOSE PHARMACOKINETIC STUDY OF SEMAGLUTIDE FOLLOWING SUBLINGUAL AND ORAL ROUTE OF ADMINISTRATION IN MALE SPRAGUE DAWLEY RAT. [00327] STUDY AIM [00328] The goal of this study was to determine the pharmacokinetics of semaglutide following oral and sublingual route of administration in male Sprague Dawley rats. [00329] MATERIALS AND METHODS [00330] This study was performed in overnight fasted male SD Rats. Rybelsus^® Semaglutide, 14 mg Tablets (Batch No.: PS6LE23) and Semaglutide B-14 mg Freeze-dried oral disintegrating Tablets (wafers) (Batch No.: B240836), were test items used in this study. Dose formulations were prepared freshly on the day of dosing. 0.5% of methyl cellulose in Milli Q water were used as the vehicle. See Tables 33 to 35 for further information on the formulations. [00331] TABLE 15: Group allocation and treatment Anim l D l [00332] Note: Permanent Id’s of Rat used in this study were Rja8167 to Rja8178. [00333] Blood samples were collected through retro orbital plexus puncture at 0 (pre- dose), 5 mins, 15 mins, 30 mins, 60 mins, 90 mins, 120 mins, 240 mins and 480 mins post dose (Total 9 time points / rat) At each time points, ~0.2 mL of blood was withdrawn and transferred into pre-labeled microcentrifuge tubes containing 20 µL per mL of blood of 200 mM K2EDTA solution as anticoagulant. Blood samples were kept on wet ice and were centrifuged immediately at 4000 rpm for 10 min at 4 °C. Plasma was separated after centrifugation. Plasma samples were transferred into pre-labeled (Animal ID No., Time point, Study No., Matrix and Group) tubes. All plasma samples were stored at -70 ± 10 °C until bioanalysis. [00334] Bioanalysis was performed using fit-for-purpose LC-MS/MS method for the quantification of semaglutide in plasma samples. [00335] The plasma pharmacokinetic parameters of semaglutide were determined from mean concentration time curves obtained following a single sublingual and oral route of administration in male SD rats. Values are expressed as Mean ± SD and n=6 rat/time point/group. [00336] Plasma pharmacokinetic parameters were calculated using standard non- compartmental analysis (Phoenix^® software, version 8.3, Certara Corporation, Mountain View, California 94040/USA) using linear trapezoidal method with linear interpolation. [00337] RESULTS AND DISCUSSION [00338] No clinical signs, mortality or morbidity was observed in treated group animals at the doses tested. [00339] The plasma pharmacokinetic parameters Semaglutide were determined from mean concentration time curves obtained following a single sublingual and oral route of administration in male Sprague Dawley rat. Values are expressed as Mean ± SD and n=6 Rat/time point/group. [00340] In Group 1 (Semaglutide wafer 10 mg/kg, Sublingual ROA to Male SD rat) time to reach peak plasma concentration (T_max) of mean was 120 min and peak plasma concentration (Cmax) of 2250 ± 2210 ng/mL. The mean exposure, AUClast and MRTlast was found to be 11000 ± 9640 ng*h/mL and 3.64 ± 0.529 h. [00341] In Group 2 (Semaglutide tablet 10 mg/kg, oral ROA to Male SD rat), time to reach peak plasma concentration (Tmax) of mean was 30 min and peak plasma concentration (Cmax) of 168 ± 244 ng/mL. The mean exposure, AUClast and MRTlast was found to be 553 ± 782 ng*h/mL and 2.75 ± 0.999 h. [00342] TABLE 16: Arithmetic Mean plasma pharmacokinetic parameters of Semaglutide following single sublingual and oral route of administration to male Sprague Dawley rat. [00343] TABLE 17: Individual plasma pharmacokinetic parameters of Semaglutide wafer following single sublingual route of administration to male Sprague Dawley rat (G1: 10 mg/kg). . 10 mg/kg/ sublingual Rat 5 5290 240 24700 3.24 [00344] TABLE 18: Individual plasma pharmacokinetic parameters of Semaglutide tablet following single oral route of administration to male Sprague Dawley rat (G2: 10 mg/kg). PK P r m t r [00345] TABLE 19: Arithmetic Mean plasma concentration time profile of Semaglutide following single Sublingual and oral route of administration to Sprague Dawley rat. 0 0 0 0 0 5 167 169 65.3 79.3 [00346] TABLE 20: Individual plasma concentrations of Semaglutide wafer following single sublingual route of administration to male Sprague Dawley rats (G1: 10 mg/kg) . . [00347] TABLE 21: Individual plasma concentrations of Semaglutide tablet following single oral route of administration to male Sprague Dawley rats (G2: 10 mg/kg) 1 g g Rat 10 0 26.5 28.4 65.7 49.6 44.5 44.6 20.8 22.1 Rat 11 0 8.48 19.7 13.3 12.7 12.7 9.29 6.86 6.01 F EXAMPLE 6 – SINGLE DOSE PHARMACOKINETIC STUDY OF SEMAGLUTIDE FOLLOWING SUBLINGUAL AND SUBCUTANEOUS ROUTE OF ADMINISTRATION IN MALE SPRAGUE DAWLEY RAT. [00348] STUDY AIM [00349] The goal of this study was to determine the pharmacokinetics of semaglutide following Sublingual and subcutaneous route of administration in male Sprague Dawley rats. [00350] MATERIALS AND METHODS [00351] This study was performed in overnight fasted animals in sublingual group and non-fasted in subcutaneous group with Male SD rats. OZEMPIC® semaglutide injection1.34mg (Batch No.: PP5K651) and semaglutide B-14 mg Freeze-dried oral disintegrating Tablets (wafers) (Batch No.: B240847 and B240846), were test items used in this study. Dose formulations were prepared freshly on the day of dosing. 0.9% Normal saline was used as diluent. See Tables 33 to 35 for further information on the formulations. [00352] TABLE 22: Group allocation and treatment l l 200 mg of wafer (~10 mg/kg) rat [00353] Note: Permanent Id’s of Rat used in this study were Rja8206 to Rja8223 [00354] Blood samples were collected through jugular vein cannulation at 0 (pre-dose), 5 mins, 15 mins, 30 mins, 60 mins, 90 mins, 120 mins, 240 mins and 480 mins post dose (Total 9 time points / rat) At each time points, ~0.2 mL of blood was withdrawn and transferred into pre-labelled microcentrifuge tubes containing 20 µL per mL of blood of 200 mM K2EDTA solution as anticoagulant. Blood samples were kept on wet ice and were centrifuged immediately at 4000 rpm for 10 min at 4 °C. Plasma was separated after centrifugation. Plasma samples were transferred into pre-labelled (Animal ID No., Time point, Study No., Matrix and Group) tubes. All plasma samples were stored at -70 ± 10 °C until bioanalysis. [00355] Bioanalysis was performed using fit-for-purpose LC-MS/MS method for the quantification of Semaglutide in plasma samples. [00356] The plasma pharmacokinetic parameters of Semaglutide were determined from mean concentration time curves obtained following a single subcutaneous and sublingual route of administration in male SD rats. Values are expressed as Mean ± SD and n=6 rat/time point/group. [00357] Plasma pharmacokinetic parameters were calculated using standard non- compartmental analysis (Phoenix^® software, version 8.3, Certara Corporation, Mountain View, California 94040/USA) using linear trapezoidal method with linear interpolation. [00358] RESULTS AND DISCUSSION [00359] No clinical signs, mortality or morbidity was observed in treated group animals at the doses tested. [00360] The plasma pharmacokinetic parameters Semaglutide were determined from mean concentration time curves obtained following a single sublingual and subcutaneous route of administration in male Sprague Dawley rat. Values are expressed as Mean ± SD and n=6 Rat/time point/group. [00361] In Group 1 (OZEMPIC^® Semaglutide injection1.34mg, 30nmol/kg, Subcutaneous ROA to Male SD rat) time to reach peak plasma concentration (T_max) of mean was 480 min and peak plasma concentration (C_max) of 586 ± 255ng/mL. The mean exposure, AUC_last and MRTlast was found to be 3430 ± 98ng*h/mL and 4.68 ± 0.222h. [00362] In Group 2 (Semaglutide Wafer (B.No.: B240847), 10 mg/kg, Sublingual ROA to Male SD rat), time to reach peak plasma concentration (T_max) of mean was 60 min and peak plasma concentration (C_max) of 972 ± 1690 ng/mL. The mean exposure, AUC_last and MRT_last was found to be 5060 ± 9830ng*h/mL and 2.9 ± 1.67h. [00363] In Group 3 (Semaglutide Wafer (B.No.: B240846), 10 mg/kg, Sublingual ROA to Male SD rat), time to reach peak plasma concentration (T_max) of mean was 90 min and peak plasma concentration (C_max) of 292 ± 160 ng/mL. The mean exposure, AUC_last and MRT_last was found to be 1200 ± 822ng*h/mL and 3.28 ± 0.945h. [00364] TABLE 23: Arithmetic Mean plasma pharmacokinetic parameters of Semaglutide following single sublingual and subcutaneous route of administration to male Sprague Dawley rat. Group 1: Group 3: al [00365] TABLE 24: Individual plasma pharmacokinetic parameters of OZEMPIC^® semaglutide injection 1.34 mg following single subcutaneous route of administration to male Sprague Dawley rat (G1: 30 nmol /kg). s . . . . [00366] TABLE 25: Individual plasma pharmacokinetic parameters of Semaglutide wafer (B.No.: B240847) following single sublingual route of administration to male Sprague Dawley rat (G2: 10 mg/kg). PK Parameters h) [00367] Note: Rat 11 considered as outlier due to anomalous behaviour within group. [00368] TABLE 26: Individual plasma pharmacokinetic parameters of Semaglutide wafer (B.No.: B240846) following single sublingual route of administration to male Sprague Dawley rat (G3: 10 mg/kg). h) . CV% 54.8 38.7 68.5 28.9 [00369] TABLE 27: Arithmetic Mean plasma concentration time profile of Semaglutide following single Subcutaneous and sublingual route of administration to Sprague Dawley rat. Group 1: Group 3: l [00370] TABLE 28: Individual plasma concentrations of OZEMPIC^® semaglutide injection 1.34 mg following single subcutaneous route of administration to male Sprague Dawley rat (G1: 30 nmol /kg). Subcutaneous Rat 5 0 14 55.5 132 223 365 365 442 681 Rat 6 0 23.8 123 425 609 746 656 828 1030 [00371] TABLE 29: Individual plasma concentrations of Semaglutide wafer (B.No.: B240847) following single sublingual route of administration to male Sprague Dawley rat (G2: 10 mg/kg). G Pl m C n ntr ti n (n /mL) [00372] Note: NA: Not Applicable & Rat 11 considered as outlier due to anomalous behaviour within group. [00373] TABLE 30: Individual plasma concentrations of Semaglutide wafer (B.No.: B240846) following single sublingual route of administration to male Sprague Dawley rat (G3: 10 mg/kg). G S ( %CV NA 41.9 58.7 78.4 75.4 78.5 67.6 80.3 87.9 G EXAMPLE 7 – SINGLE DOSE PHARMACOKINETIC STUDY OF COMBINATION LIRAGLUTIDE/DAPAGLIFLOZIN SUBLINGUAL WAFER IN MALE SPRAGUE DAWLEY RATS. [00374] STUDY AIM [00375] To determine the pharmacokinetics of a combination Liraglutide and Dapagliflozin sublingual wafer in male Sprague Dawley Rat. [00376] MATERIALS AND METHODS [00377] Test System [00378] Species: Rat; Strain: Sprague Dawley; Sex: Male; Rationale: Sprague Dawley rat is commonly used rodent species in the pharmacokinetic evaluation of drugs and acceptable to the regulatory authorities; Total number of animals: 18 Rats (6 rats/group); Age/ Body Weight at study initiation: 7-10 weeks, 250- 350 g; Veterinary Examination: Prior to the final assignment to the study, animals will be subjected to complete veterinary health examination to ensure that the selected animals are in a good state of health; Animal Identification: Animals will be uniquely identified by individual tail marking with a permanent marker along with cage card; Acclimatization: On receipt from supplier, the animals will be examined for any external signs of ill health and aberrant behavior prior to acceptance. After health examination, animals will be quarantined for one week under test conditions and then acclimatized for a minimum of 5 days in study room. Only animals without any visible signs of illness will be used for the study; Animal catheterization: Under Ketamine and Xylazine anesthesia, all animals will be cannulated in right external jugular vein. Rats will be surgically implanted with a catheter (jugular vein, Polyethylene-50 tubing attached to Polyurethane-40 catheter) for blood collection. Rats will be allowed to recover for minimum of 48 h after cannulation, before inclusion in study and drug administration. General animal health and cannula patency will be confirmed prior to dose administration. [00379] Husbandry [00380] Housing Conditions: Standard laboratory conditions, temperature will be maintained between 22±3°C and relative humidity between 30–70 % under a 12 h light/dark cycle. Air changes of 12-15 times per hour via a centrally placed air intake and peripheral ventilators will be maintained. Accommodation: Each animal will be placed in individual polycarbonate cage with stainless steel grill top with facilities for feed and water bottle and bedding of clean corn cob. Feed: Hypro pelleted rodent feed will be provided ad libitum. All group rats will be fasted overnight. No feed will be provided. Water: Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier will be provided ad libitum in polycarbonate bottles with stainless steel sipper tubes. All rats will have access to water ad libitum. Animal handling: Experiment will be carried out by qualified & trained scientific personnel (trained in animal handling, drug administration and experimentation). Body weight: On the day of dosing. Clinical signs: Animals will be observed for any apparent clinical signs of ill-health and toxicity during study duration. [00381] Dose Formulation Preparation [00382] The dose formulation will be prepared freshly on the day of dosing. [00383] TABLE 31: Group Allocation and Treatment [00384] Note: See Tables 33 to 35 for further information on the formulations. Liraglutide SL wafer and Liraglutide SC injection only rat pK data are being generated in another study. These data will be used for comparison to data generated in this study. [00385] Dose administration [00386] Wafers will be crushed and weighed on an accurate balance and placed in the sublingual space under isoflurane anesthesia for 4-5 min followed by up to 1-2 drops of water to assist in disintegration (use minimal amount required to disintegrate wafers). [00387] Note: The sublingual mucosa moistness will be ensured prior to administering the SL wafer by administering a small quantity of water into the SL space, just prior to anesthesia. [00388] Subcutaneous administration will be on the dorsal side towards Cranial. [00389] Blood collection and storage of samples [00390] Site of blood collection: Jugular vein via cannulation; Anticoagulant:K2EDTA (20 µL of 200 mM solution per 1 mL of blood); Blood collection time points: 0 (pre-dose), 0.083 h, 0.25 h, 0.5 h, 1 h, 2 h, 4h, 8 h and 24 h post dose (Total 9 time points/rat); Volume of blood collected: ~0.2 mL at each time points from each rat; Blood sampling procedure: Serial sampling [00391] Blood centrifugation time: 4000 rpm for 10 minutes at 4 °C; Matrix: Plasma; Matrix storage: -70 ± 10 °C until analysis; Matrix labeling details: Study number, Group, Animal ID, and Time point; Note: 1. Blood samples will be kept on wet ice until centrifugation. Centrifugation will be done within 30 minutes of collection and plasma will be checked for hemolysis. If samples are hemolyzed, another sample will be taken as soon as possible.2. Prepared dose formulation will be discarded after the completion of in-life phase. 3. On completion of the last blood sampling, animals will be sacrificed, and carcasses discarded. [00392] Bioanalysis [00393] Matrix: Plasma. Analyte: Liraglutide and Dapagliflozin. Bioanalysis will be performed by fit-for-purpose analytical method using LC-MS/MS. Upon finalization of study report, remaining biological study samples will be discarded. [00394] Pharmacokinetic data and analysis and evaluation [00395] Pharmacokinetic Software: Phoenix® Software, version 8.3, USA. [00396] Pharmacokinetic Parameters: C0, Cmax, Tmax, AUC0-t, AUC0-∞, Kel, T1/2, Vd, Vd,/F, Cl, Cl/F and MRTlast. [00397] RESULTS [00398] The study is to determine the relative bioavailability of a novel formulation of a sublingual lyophilised combination product containing liraglutide and dapagliflozin compared to administering both liraglutide injection subcutaneously and dapagliflozin tablets orally, as well as dapagliflozin in a sublingual wafer. We expect the relative bioavailability to be in the range of 2-50% for liraglutide and 70-95% for dapagliflozin. In addition, we expect to see more rapid absorption into plasma following administration with the sublingual wafer compared to subcutaneous injection. [00399] DISCUSSION [00400] These results represent the first data available on the relative bioavailability of sublingual administration of liraglutide and dapagliflozin. Obtaining systemic absorption of liraglutide via sublingual administration with this novel wafer creates the potential for a non- injectable formulation of liraglutide. At present, liraglutide is only available as an injectable product. Although Dapagliflozin is available as an oral tablet today, there is no combination product of both liraglutide and dapagliflozin. These combination of these two drug classes is expected to have greater efficacy than either product alone due to the complementary mechanisms of action. Such a product would be non-invasive, easier to use, convenient and improve patient compliance. H EXAMPLE 8 – SINGLE DOSE PHARMACOKINETIC STUDY OF COMBINATION SEMAGLUTIDE/DAPAGLIFLOZIN SUBLINGUAL WAFER IN MALE SPRAGUE DAWLEY RATS. [00401] STUDY AIM [00402] To determine the pharmacokinetics of a combination Semaglutide and Dapagliflozin sublingual wafer in male Sprague Dawley Rat. [00403] MATERIALS AND METHODS [00404] Test System [00405] Species: Rat; Strain: Sprague Dawley; Sex: Male; Rationale: Sprague Dawley rat is commonly used rodent species in the pharmacokinetic evaluation of drugs and acceptable to the regulatory authorities; Total number of animals: 18 Rats (6 rats/group); Age/ Body Weight at study initiation: 7-10 weeks, 250- 350 g; Veterinary Examination: Prior to the final assignment to the study, animals will be subjected to complete veterinary health examination to ensure that the selected animals are in a good state of health; Animal Identification: Animals will be uniquely identified by individual tail marking with a permanent marker along with cage card; Acclimatization: On receipt from supplier, the animals will be examined for any external signs of ill health and aberrant behavior prior to acceptance. After health examination, animals will be quarantined for one week under test conditions and then acclimatized for a minimum of 5 days in study room. Only animals without any visible signs of illness will be used for the study; Animal catheterization: Under Ketamine and Xylazine anesthesia, all animals will be cannulated in right external jugular vein. Rats will be surgically implanted with a catheter (jugular vein, Polyethylene-50 tubing attached to Polyurethane-40 catheter) for blood collection. Rats will be allowed to recover for minimum of 48 h after cannulation, before inclusion in study and drug administration. General animal health and cannula patency will be confirmed prior to dose administration. [00406] Husbandry [00407] Housing Conditions: Standard laboratory conditions, temperature will be maintained between 22±3°C and relative humidity between 30–70 % under a 12 h light/dark cycle. Air changes of 12-15 times per hour via a centrally placed air intake and peripheral ventilators will be maintained. Accommodation: Each animal will be placed in individual polycarbonate cage with stainless steel grill top with facilities for feed and water bottle and bedding of clean corn cob. Feed: Hypro pelleted rodent feed will be provided ad libitum. All group rats will be fasted overnight. No feed will be provided. Water: Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier will be provided ad libitum in polycarbonate bottles with stainless steel sipper tubes. All rats will have access to water ad libitum. Animal handling: Experiment will be carried out by qualified & trained scientific personnel (trained in animal handling, drug administration and experimentation). Body weight: On the day of dosing. Clinical signs: Animals will be observed for any apparent clinical signs of ill-health and toxicity during study duration. [00408] Dose Formulation Preparation [00409] The dose formulation will be prepared freshly on the day of dosing. [00410] TABLE 31: Group Allocation and Treatment [00411] Note: See Tables 33 to 35 for further information on the formulations. Semaglutide SL wafer and Semaglutide SC injection only rat pK data are being generated in another study. These data will be used for comparison to data generated in this study. [00412] Dose administration [00413] Wafers will be crushed and weighed on an accurate balance and placed in the sublingual space under isoflurane anesthesia for 4-5 min followed by up to 1-2 drops of water to assist in disintegration (use minimal amount required to disintegrate wafers). [00414] Note: The sublingual mucosa moistness will be ensured prior to administering the SL wafer by administering a small quantity of water into the SL space, just prior to anesthesia. [00415] Subcutaneous administration will be on the dorsal side towards Cranial. [00416] Blood collection and storage of samples [00417] Site of blood collection: Jugular vein via cannulation; Anticoagulant:K2EDTA (20 µL of 200 mM solution per 1 mL of blood); Blood collection time points: 0 (pre-dose), 0.083 h, 0.25 h, 0.5 h, 1 h, 2 h, 4h, 8 h and 24 h post dose (Total 9 time points/rat); Volume of blood collected: ~0.2 mL at each time points from each rat; Blood sampling procedure: Serial sampling [00418] Blood centrifugation time: 4000 rpm for 10 minutes at 4 °C; Matrix: Plasma; Matrix storage: -70 ± 10 °C until analysis; Matrix labeling details: Study number, Group, Animal ID, and Time point; Note: 1. Blood samples will be kept on wet ice until centrifugation. Centrifugation will be done within 30 minutes of collection and plasma will be checked for hemolysis. If samples are hemolyzed, another sample will be taken as soon as possible.2. Prepared dose formulation will be discarded after the completion of in-life phase. 3. On completion of the last blood sampling, animals will be sacrificed, and carcasses discarded. [00419] Bioanalysis [00420] Matrix: Plasma. Analyte: Semaglutide and Dapagliflozin. Bioanalysis will be performed by fit-for-purpose analytical method using LC-MS/MS. Upon finalization of study report, remaining biological study samples will be discarded. [00421] Pharmacokinetic data and analysis and evaluation [00422] Pharmacokinetic Software: Phoenix® Software, version 8.3, USA. [00423] Pharmacokinetic Parameters: C0, Cmax, Tmax, AUC0-t, AUC0-∞, Kel, T1/2, Vd, Vd,/F, Cl, Cl/F and MRTlast. [00424] RESULTS [00425] The study is to determine the relative bioavailability of a novel formulation of a sublingual lyophilised combination product containing semaglutide and dapagliflozin compared to administering both semaglutide and dapagliflozin tablets orally. We expect the relative bioavailability to be in the range of 70-95% for dapagliflozin. We expect the relative bioavailability of semaglutide with the sublingual wafer to be approximately 20 times that of oral semaglutide (Rybelsus®) based on previous pharmacokinetic data in rats. In addition, we expect to see more rapid absorption into plasma following administration with the sublingual wafer compared to oral tables. [00426] DISCUSSION [00427] These results represent the first data available on the relative bioavailability of sublingual administration of semaglutide and dapagliflozin. Obtaining systemic absorption of semaglutide via sublingual administration with this novel wafer creates the potential for a more effective non-injectable formulation of semaglutide than the existing oral tablet, Rybelsus® Although Dapagliflozin is available as an oral tablet today, there is no combination product of both semaglutide and dapagliflozin. These combination of these two drug classes is expected to have greater efficacy than either product alone due to the complementary mechanisms of action. Such a product would be non-invasive, easier to use, convenient and improve patient compliance. I EXAMPLE 9 – SINGLE DOSE PHARMACOKINETIC STUDY OF SEMAGLUTIDE SUBLINGUAL WAFER IN MALE SPRAGUE DAWLEY RATS. [00428] STUDY AIM [00429] To determine the pharmacokinetics of Semaglutide sublingual wafer in male Sprague Dawley Rat. [00430] MATERIALS AND METHODS [00431] A further study was conducted using the methods described above and standard methods described in the art. [00432] It was a single-dose pK study in Sprague-Dawley rats (n=30, 7-10 weeks old, weighing 300-350g). Animals were anaesthetised during sublingual administration for ~3 minutes. Venous blood samples were obtained over 8-hour period. Plasma samples were analysed by LC-MS/MS. [00433] The treatment arms were as follows: [00434] SL Wafer Formulation A, 10mg/kg (n=6) [00435] SL Wafer Formulation B, 10mg/kg (n=6) [00436] SL Wafer Formulation C, 10mg/kg (n=6) [00437] PO Rybelsus® tablet, 10mg/kg (n=6) [00438] S/C Ozempic®, 0.12mg/kg (n=6) [00439] See Tables 33 to 35 for further information on the formulations. [00440] RESULTS [00441] The results are presented in Figure 9. Formulation A administration resulted in ~20x higher bioavailability and lower variability (CV 87% v 141%) than Rybelsus® oral tablet in Sprague-Dawley rats. See Tables 33 to 35 for further information on the formulations. [00442] TABLE 32: Pharmacokinetic results [00443] DISCUSSION [00444] These results demonstrate superior pharmacokinetics of all three formulations of a novel sublingual semaglutide wafer (see Table 32). The sublingual formulation A demonstrated to most superior pharmacokinetic profile with a bioavailability of approximately 20 times that of oral semaglutide tablet, Rybelsus® in Sprague-Dawley rats. Compared to subcutaneous injection, the relative bioavailability of this sublingual formulation was approximately 4%. These results show the potential for a more effective non-invasive formulation of semaglutide compared to Rybelsus®. This could result in the use of a lower dosage whilst maintaining efficacy and with the potential for a lower side effect profile. J EXAMPLE 10 – FORMULATIONS USED IN EXAMPLES. [00445] FORMULATIONS [00446] Please see Tables 33 to 36 below for the formulations used in the studies described above. [00447] TABLE 33: Semaglutide formula A, B, C . . . p 16 Sucralose 9.0 9.2 9.0 [00448] The range values are: 1. semaglutide 2mg to 50 mg per wafer; 2. SNAC value 0.1% to 80%; 3. Sodium deoxycholate 0.1% to 20%; 4. Soy lecithin 0% to 30%; and 5. pH buffer from pH 5 to 9 using either TRIS or phosphate buffer. [00449] TABLE 34: Liraglutide/Dapagliflozin and Dapagliflozin formulation i . . 13 Sodium deoxycholate See range. See range. [00450] The range values are: 1. Liraglutide 2.5mg to 50 mg per wafer; 2. Dapagliflozin 2.5 to 30 mg; 3. TPGS (d-α-tocopheryl polyethylene glycol succinate) penetrant/surfactant 0.1%; to 20%; 4. Sodium deoxycholate 0.1% to 20%. [00451] TABLE 35: Semaglutide dapagliflozin formulation 1 g . 12 Soy lecithin See range. [00452] The range values are: 1. Semaglutide 2mg to 50 mg per wafer; 2. Dapagliflozin 2.5 to 30 mg; 3. SNAC 0.1% to 20%; 4. Soy lecithin 0% to 30%; and 5. Sodium deoxycholate 0.1% to 20%. [00453] THE PREFERRED RANGES AND VALUES IN THE FORMULATIONS PRESENTED IN TABLES 33, 34 AND 35 ARE AS FOLLOWS. [00454] Semaglutide - 2.5mg to 50 mg per wafer, including: 2.4mg; 2.5mg; 2.6mg; 2.7mg; 2.8mg; 2.9mg; 3.0mg; 3.1mg; 3.2mg; 3.3mg; 3.4mg; 3.5mg; 3.6mg; 3.7mg; 3.8mg; 3.9mg; 4.0mg; 4.1mg; 4.2mg; 4.3mg; 4.4mg; 4.5mg; 4.6mg; 4.7mg; 4.8mg; 4.9mg; 5.0mg; 5.1mg; 5.2mg; 5.3mg; 5.4mg; 5.5mg; 5.6mg; 5.7mg; 5.8mg; 5.9mg; 6.0mg; 6.1mg; 6.2mg; 6.3mg; 6.4mg; 6.5mg; 6.6mg; 6.7mg; 6.8mg; 6.9mg; 7.0mg; 7.1mg; 7.2mg; 7.3mg; 7.4mg; 7.5mg; 7.6mg; 7.7mg; 7.8mg; 7.9mg; 8.0mg; 8.1mg; 8.2mg; 8.3mg; 8.4mg; 8.5mg; 8.6mg; 8.7mg; 8.8mg; 8.9mg; 9.0mg; 9.1mg; 9.2mg; 9.3mg; 9.4mg; 9.5mg; 9.6mg; 9.7mg; 9.8mg; 9.9mg; 10.0mg; 10.1mg; 10.2mg; 10.3mg; 10.4mg; 10.5mg; 10.6mg; 10.7mg; 10.8mg; 10.9mg; 11.0mg; 11.1mg; 11.2mg; 11.3mg; 11.4mg; 11.5mg; 11.6mg; 11.7mg; 11.8mg; 11.9mg; 12.0mg; 12.1mg; 12.2mg; 12.3mg; 12.4mg; 12.5mg; 12.6mg; 12.7mg; 12.8mg; 12.9mg; 13.0mg; 13.1mg; 13.2mg; 13.3mg; 13.4mg; 13.5mg; 13.6mg; 13.7mg; 13.8mg; 13.9mg; 14.0mg; 14.1mg; 14.2mg; 14.3mg; 14.4mg; 14.5mg; 14.6mg; 14.7mg; 14.8mg; 14.9mg; 15.0mg; 15.1mg; 15.2mg; 15.3mg; 15.4mg; 15.5mg; 15.6mg; 15.7mg; 15.8mg; 15.9mg; 16.0mg; 16.1mg; 16.2mg; 16.3mg; 16.4mg; 16.5mg; 16.6mg; 16.7mg; 16.8mg; 16.9mg; 17.0mg; 17.1mg; 17.2mg; 17.3mg; 17.4mg; 17.5mg; 17.6mg; 17.7mg; 17.8mg; 17.9mg; 18.0mg; 18.1mg; 18.2mg; 18.3mg; 18.4mg; 18.5mg; 18.6mg; 18.7mg; 18.8mg; 18.9mg; 19.0mg; 19.1mg; 19.2mg; 19.3mg; 19.4mg; 19.5mg; 19.6mg; 19.7mg; 19.8mg; 19.9mg; 20.0mg; 20.1mg; 20.2mg; 20.3mg; 20.4mg; 20.5mg; 20.6mg; 20.7mg; 20.8mg; 20.9mg; 21.0mg; 21.1mg; 21.2mg; 21.3mg; 21.4mg; 21.5mg; 21.6mg; 21.7mg; 21.8mg; 21.9mg; 22.0mg; 22.1mg; 22.2mg; 22.3mg; 22.4mg; 22.5mg; 22.6mg; 22.7mg; 22.8mg; 22.9mg; 23.0mg; 23.1mg; 23.2mg; 23.3mg; 23.4mg; 23.5mg; 23.6mg; 23.7mg; 23.8mg; 23.9mg; 24.0mg; 24.1mg; 24.2mg; 24.3mg; 24.4mg; 24.5mg; 24.6mg; 24.7mg; 24.8mg; 24.9mg; 25.0mg; 25.1mg; 25.2mg; 25.3mg; 25.4mg; 25.5mg; 25.6mg; 25.7mg; 25.8mg; 25.9mg; 26.0mg; 26.1mg; 26.2mg; 26.3mg; 26.4mg; 26.5mg; 26.6mg; 26.7mg; 26.8mg; 26.9mg; 27.0mg; 27.1mg; 27.2mg; 27.3mg; 27.4mg; 27.5mg; 27.6mg; 27.7mg; 27.8mg; 27.9mg; 28.0mg; 28.1mg; 28.2mg; 28.3mg; 28.4mg; 28.5mg; 28.6mg; 28.7mg; 28.8mg; 28.9mg; 29.0mg; 29.1mg; 29.2mg; 29.3mg; 29.4mg; 29.5mg; 29.6mg; 29.7mg; 29.8mg; 29.9mg; 30.0mg; 30.1mg; 30.2mg; 30.3mg; 30.4mg; 30.5mg; 30.6mg; 30.7mg; 30.8mg; 30.9mg; 31.0mg; 31.1mg; 31.2mg; 31.3mg; 31.4mg; 31.5mg; 31.6mg; 31.7mg; 31.8mg; 31.9mg; 32.0mg; 32.1mg; 32.2mg; 32.3mg; 32.4mg; 32.5mg; 32.6mg; 32.7mg; 32.8mg; 32.9mg; 33.0mg; 33.1mg; 33.2mg; 33.3mg; 33.4mg; 33.5mg; 33.6mg; 33.7mg; 33.8mg; 33.9mg; 34.0mg; 34.1mg; 34.2mg; 34.3mg; 34.4mg; 34.5mg; 34.6mg; 34.7mg; 34.8mg; 34.9mg; 35.0mg; 35.1mg; 35.2mg; 35.3mg; 35.4mg; 35.5mg; 35.6mg; 35.7mg; 35.8mg; 35.9mg; 36.0mg; 36.1mg; 36.2mg; 36.3mg; 36.4mg; 36.5mg; 36.6mg; 36.7mg; 36.8mg; 36.9mg; 37.0mg; 37.1mg; 37.2mg; 37.3mg; 37.4mg; 37.5mg; 37.6mg; 37.7mg; 37.8mg; 37.9mg; 38.0mg; 38.1mg; 38.2mg; 38.3mg; 38.4mg; 38.5mg; 38.6mg; 38.7mg; 38.8mg; 38.9mg; 39.0mg; 39.1mg; 39.2mg; 39.3mg; 39.4mg; 39.5mg; 39.6mg; 39.7mg; 39.8mg; 39.9mg; 40.0mg; 40.1mg; 40.2mg; 40.3mg; 40.4mg; 40.5mg; 40.6mg; 40.7mg; 40.8mg; 40.9mg; 41.0mg; 41.1mg; 41.2mg; 41.3mg; 41.4mg; 41.5mg; 41.6mg; 41.7mg; 41.8mg; 41.9mg; 42.0mg; 42.1mg; 42.2mg; 42.3mg; 42.4mg; 42.5mg; 42.6mg; 42.7mg; 42.8mg; 42.9mg; 43.0mg; 43.1mg; 43.2mg; 43.3mg; 43.4mg; 43.5mg; 43.6mg; 43.7mg; 43.8mg; 43.9mg; 44.0mg; 44.1mg; 44.2mg; 44.3mg; 44.4mg; 44.5mg; 44.6mg; 44.7mg; 44.8mg; 44.9mg; 45.0mg; 45.1mg; 45.2mg; 45.3mg; 45.4mg; 45.5mg; 45.6mg; 45.7mg; 45.8mg; 45.9mg; 46.0mg; 46.1mg; 46.2mg; 46.3mg; 46.4mg; 46.5mg; 46.6mg; 46.7mg; 46.8mg; 46.9mg; 47.0mg; 47.1mg; 47.2mg; 47.3mg; 47.4mg; 47.5mg; 47.6mg; 47.7mg; 47.8mg; 47.9mg; 48.0mg; 48.1mg; 48.2mg; 48.3mg; 48.4mg; 48.5mg; 48.6mg; 48.7mg; 48.8mg; 48.9mg; 49.0mg; 49.1mg; 49.2mg; 49.3mg; 49.4mg; 49.5mg; 49.6mg; 49.7mg; 49.8mg; 49.9mg; and 50.0mg. [00455] Dapagliflozin - 2.5mg to 30 mg per wafer, including: 2.4mg; 2.5mg; 2.6mg; 2.7mg; 2.8mg; 2.9mg; 3.0mg; 3.1mg; 3.2mg; 3.3mg; 3.4mg; 3.5mg; 3.6mg; 3.7mg; 3.8mg; 3.9mg; 4.0mg; 4.1mg; 4.2mg; 4.3mg; 4.4mg; 4.5mg; 4.6mg; 4.7mg; 4.8mg; 4.9mg; 5.0mg; 5.1mg; 5.2mg; 5.3mg; 5.4mg; 5.5mg; 5.6mg; 5.7mg; 5.8mg; 5.9mg; 6.0mg; 6.1mg; 6.2mg; 6.3mg; 6.4mg; 6.5mg; 6.6mg; 6.7mg; 6.8mg; 6.9mg; 7.0mg; 7.1mg; 7.2mg; 7.3mg; 7.4mg; 7.5mg; 7.6mg; 7.7mg; 7.8mg; 7.9mg; 8.0mg; 8.1mg; 8.2mg; 8.3mg; 8.4mg; 8.5mg; 8.6mg; 8.7mg; 8.8mg; 8.9mg; 9.0mg; 9.1mg; 9.2mg; 9.3mg; 9.4mg; 9.5mg; 9.6mg; 9.7mg; 9.8mg; 9.9mg; 10.0mg; 10.1mg; 10.2mg; 10.3mg; 10.4mg; 10.5mg; 10.6mg; 10.7mg; 10.8mg; 10.9mg; 11.0mg; 11.1mg; 11.2mg; 11.3mg; 11.4mg; 11.5mg; 11.6mg; 11.7mg; 11.8mg; 11.9mg; 12.0mg; 12.1mg; 12.2mg; 12.3mg; 12.4mg; 12.5mg; 12.6mg; 12.7mg; 12.8mg; 12.9mg; 13.0mg; 13.1mg; 13.2mg; 13.3mg; 13.4mg; 13.5mg; 13.6mg; 13.7mg; 13.8mg; 13.9mg; 14.0mg; 14.1mg; 14.2mg; 14.3mg; 14.4mg; 14.5mg; 14.6mg; 14.7mg; 14.8mg; 14.9mg; 15.0mg; 15.1mg; 15.2mg; 15.3mg; 15.4mg; 15.5mg; 15.6mg; 15.7mg; 15.8mg; 15.9mg; 16.0mg; 16.1mg; 16.2mg; 16.3mg; 16.4mg; 16.5mg; 16.6mg; 16.7mg; 16.8mg; 16.9mg; 17.0mg; 17.1mg; 17.2mg; 17.3mg; 17.4mg; 17.5mg; 17.6mg; 17.7mg; 17.8mg; 17.9mg; 18.0mg; 18.1mg; 18.2mg; 18.3mg; 18.4mg; 18.5mg; 18.6mg; 18.7mg; 18.8mg; 18.9mg; 19.0mg; 19.1mg; 19.2mg; 19.3mg; 19.4mg; 19.5mg; 19.6mg; 19.7mg; 19.8mg; 19.9mg; 20.0mg; 20.1mg; 20.2mg; 20.3mg; 20.4mg; 20.5mg; 20.6mg; 20.7mg; 20.8mg; 20.9mg; 21.0mg; 21.1mg; 21.2mg; 21.3mg; 21.4mg; 21.5mg; 21.6mg; 21.7mg; 21.8mg; 21.9mg; 22.0mg; 22.1mg; 22.2mg; 22.3mg; 22.4mg; 22.5mg; 22.6mg; 22.7mg; 22.8mg; 22.9mg; 23.0mg; 23.1mg; 23.2mg; 23.3mg; 23.4mg; 23.5mg; 23.6mg; 23.7mg; 23.8mg; 23.9mg; 24.0mg; 24.1mg; 24.2mg; 24.3mg; 24.4mg; 24.5mg; 24.6mg; 24.7mg; 24.8mg; 24.9mg; 25.0mg; 25.1mg; 25.2mg; 25.3mg; 25.4mg; 25.5mg; 25.6mg; 25.7mg; 25.8mg; 25.9mg; 26.0mg; 26.1mg; 26.2mg; 26.3mg; 26.4mg; 26.5mg; 26.6mg; 26.7mg; 26.8mg; 26.9mg; 27.0mg; 27.1mg; 27.2mg; 27.3mg; 27.4mg; 27.5mg; 27.6mg; 27.7mg; 27.8mg; 27.9mg; 28.0mg; 28.1mg; 28.2mg; 28.3mg; 28.4mg; 28.5mg; 28.6mg; 28.7mg; 28.8mg; 28.9mg; 29.0mg; 29.1mg; 29.2mg; 29.3mg; 29.4mg; 29.5mg; 29.6mg; 29.7mg; 29.8mg; 29.9mg; and 30.0mg. [00456] Liraglutide - 2.5mg to 50 mg per wafer, including: 2.4mg; 2.5mg; 2.6mg; 2.7mg; 2.8mg; 2.9mg; 3.0mg; 3.1mg; 3.2mg; 3.3mg; 3.4mg; 3.5mg; 3.6mg; 3.7mg; 3.8mg; 3.9mg; 4.0mg; 4.1mg; 4.2mg; 4.3mg; 4.4mg; 4.5mg; 4.6mg; 4.7mg; 4.8mg; 4.9mg; 5.0mg; 5.1mg; 5.2mg; 5.3mg; 5.4mg; 5.5mg; 5.6mg; 5.7mg; 5.8mg; 5.9mg; 6.0mg; 6.1mg; 6.2mg; 6.3mg; 6.4mg; 6.5mg; 6.6mg; 6.7mg; 6.8mg; 6.9mg; 7.0mg; 7.1mg; 7.2mg; 7.3mg; 7.4mg; 7.5mg; 7.6mg; 7.7mg; 7.8mg; 7.9mg; 8.0mg; 8.1mg; 8.2mg; 8.3mg; 8.4mg; 8.5mg; 8.6mg; 8.7mg; 8.8mg; 8.9mg; 9.0mg; 9.1mg; 9.2mg; 9.3mg; 9.4mg; 9.5mg; 9.6mg; 9.7mg; 9.8mg; 9.9mg; 10.0mg; 10.1mg; 10.2mg; 10.3mg; 10.4mg; 10.5mg; 10.6mg; 10.7mg; 10.8mg; 10.9mg; 11.0mg; 11.1mg; 11.2mg; 11.3mg; 11.4mg; 11.5mg; 11.6mg; 11.7mg; 11.8mg; 11.9mg; 12.0mg; 12.1mg; 12.2mg; 12.3mg; 12.4mg; 12.5mg; 12.6mg; 12.7mg; 12.8mg; 12.9mg; 13.0mg; 13.1mg; 13.2mg; 13.3mg; 13.4mg; 13.5mg; 13.6mg; 13.7mg; 13.8mg; 13.9mg; 14.0mg; 14.1mg; 14.2mg; 14.3mg; 14.4mg; 14.5mg; 14.6mg; 14.7mg; 14.8mg; 14.9mg; 15.0mg; 15.1mg; 15.2mg; 15.3mg; 15.4mg; 15.5mg; 15.6mg; 15.7mg; 15.8mg; 15.9mg; 16.0mg; 16.1mg; 16.2mg; 16.3mg; 16.4mg; 16.5mg; 16.6mg; 16.7mg; 16.8mg; 16.9mg; 17.0mg; 17.1mg; 17.2mg; 17.3mg; [00457] Soy lecithin - 0% to 30% including: 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; 0.6%; 0.7%; 0.8%; 0.9%; 1.0%; 1.1%; 1.2%; 1.3%; 1.4%; 1.5%; 1.6%; 1.7%; 1.8%; 1.9%; 2.0%; 2.1%; 2.2%; 2.3%; 2.4%; 2.5%; 2.6%; 2.7%; 2.8%; 2.9%; 3.0%; 3.1%; 3.2%; 3.3%; 3.4%; 3.5%; 3.6%; 3.7%; 3.8%; 3.9%; 4.0%; 4.1%; 4.2%; 4.3%; 4.4%; 4.5%; 4.6%; 4.7%; 4.8%; 4.9%; 5.0%; 5.1%; 5.2%; 5.3%; 5.4%; 5.5%; 5.6%; 5.7%; 5.8%; 5.9%; 6.0%; 6.1%; 6.2%; 6.3%; 6.4%; 6.5%; 6.6%; 6.7%; 6.8%; 6.9%; 7.0%; 7.1%; 7.2%; 7.3%; 7.4%; 7.5%; 7.6%; 7.7%; 7.8%; 7.9%; 8.0%; 8.1%; 8.2%; 8.3%; 8.4%; 8.5%; 8.6%; 8.7%; 8.8%; 8.9%; 9.0%; 9.1%; 9.2%; 9.3%; 9.4%; 9.5%; 9.6%; 9.7%; 9.8%; 9.9%; 10.0%; 10.1%; 10.2%; 10.3%; 10.4%; 10.5%; 10.6%; 10.7%; 10.8%; 10.9%; 11.0%; 11.1%; 11.2%; 11.3%; 11.4%; 11.5%; 11.6%; 11.7%; 11.8%; 11.9%; 12.0%; 12.1%; 12.2%; 12.3%; 12.4%; 12.5%; 12.6%; 12.7%; 12.8%; 12.9%; 13.0%; 13.1%; 13.2%; 13.3%; 13.4%; 13.5%; 13.6%; 13.7%; 13.8%; 13.9%; 14.0%; 14.1%; 14.2%; 14.3%; 14.4%; 14.5%; 14.6%; 14.7%; 14.8%; 14.9%; 15.0%; 15.1%; 15.2%; 15.3%; 15.4%; 15.5%; 15.6%; 15.7%; 15.8%; 15.9%; 16.0%; 16.1%; 16.2%; 16.3%; 16.4%; 16.5%; 16.6%; 16.7%; 16.8%; 16.9%; 17.0%; 17.1%; 17.2%; 17.3%; 17.4%; 17.5%; 17.6%; 17.7%; 17.8%; 17.9%; 18.0%; 18.1%; 18.2%; 18.3%; 18.4%; 18.5%; 18.6%; 18.7%; 18.8%; 18.9%; 19.0%; 19.1%; 19.2%; 19.3%; 19.4%; 19.5%; 19.6%; 19.7%; 19.8%; 19.9%; and 20.0%; 20.1%; 20.2%; 20.3%; 20.4%; 20.5%; 20.6%; 20.7%; 20.8%; 20.9%; 21.0%; 21.1%; 21.2%; 21.3%; 21.4%; 21.5%; 21.6%; 21.7%; 21.8%; 21.9%; 22.0%; 22.1%; 22.2%; 22.3%; 22.4%; 22.5%; 22.6%; 22.7%; 22.8%; 22.9%; 23.0%; 23.1%; 23.2%; 23.3%; 23.4%; 23.5%; 23.6%; 23.7%; 23.8%; 23.9%; 24.0%; 24.1%; 24.2%; 24.3%; 24.4%; 24.5%; 24.6%; 24.7%; 24.8%; 24.9%; 25.0%; 25.1%; 25.2%; 25.3%; 25.4%; 25.5%; 25.6%; 25.7%; 25.8%; 25.9%; 26.0%; 26.1%; 26.2%; 26.3%; 26.4%; 26.5%; 26.6%; 26.7%; 26.8%; 26.9%; 27.0%; 27.1%; 27.2%; 27.3%; 27.4%; 27.5%; 27.6%; 27.7%; 27.8%; 27.9%; 28.0%; 28.1%; 28.2%; 28.3%; 28.4%; 28.5%; 28.6%; 28.7%; 28.8%; 28.9%; 29.0%; 29.1%; 29.2%; 29.3%; 29.4%; 29.5%; 29.6%; 29.7%; 29.8%; 29.9%; and 30.0%. [00458] Sodium deoxycholate - 0.1% to 20%, including: 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; 0.6%; 0.7%; 0.8%; 0.9%; 1.0%; 1.1%; 1.2%; 1.3%; 1.4%; 1.5%; 1.6%; 1.7%; 1.8%; 1.9%; 2.0%; 2.1%; 2.2%; 2.3%; 2.4%; 2.5%; 2.6%; 2.7%; 2.8%; 2.9%; 3.0%; 3.1%; 3.2%; 3.3%; 3.4%; 3.5%; 3.6%; 3.7%; 3.8%; 3.9%; 4.0%; 4.1%; 4.2%; 4.3%; 4.4%; 4.5%; 4.6%; 4.7%; 4.8%; 4.9%; 5.0%; 5.1%; 5.2%; 5.3%; 5.4%; 5.5%; 5.6%; 5.7%; 5.8%; 5.9%; 6.0%; 6.1%; 6.2%; 6.3%; 6.4%; 6.5%; 6.6%; 6.7%; 6.8%; 6.9%; 7.0%; 7.1%; 7.2%; 7.3%; 7.4%; 7.5%; 7.6%; 7.7%; 7.8%; 7.9%; 8.0%; 8.1%; 8.2%; 8.3%; 8.4%; 8.5%; 8.6%; 8.7%; 8.8%; 8.9%; 9.0%; 9.1%; 9.2%; 9.3%; 9.4%; 9.5%; 9.6%; 9.7%; 9.8%; 9.9%; 10.0%; 10.1%; 10.2%; 10.3%; 10.4%; 10.5%; 10.6%; 10.7%; 10.8%; 10.9%; 11.0%; 11.1%; 11.2%; 11.3%; 11.4%; 11.5%; 11.6%; 11.7%; 11.8%; 11.9%; 12.0%; 12.1%; 12.2%; 12.3%; 12.4%; 12.5%; 12.6%; 12.7%; 12.8%; 12.9%; 13.0%; 13.1%; 13.2%; 13.3%; 13.4%; 13.5%; 13.6%; 13.7%; 13.8%; 13.9%; 14.0%; 14.1%; 14.2%; 14.3%; 14.4%; 14.5%; 14.6%; 14.7%; 14.8%; 14.9%; 15.0%; 15.1%; 15.2%; 15.3%; 15.4%; 15.5%; 15.6%; 15.7%; 15.8%; 15.9%; 16.0%; 16.1%; 16.2%; 16.3%; 16.4%; 16.5%; 16.6%; 16.7%; 16.8%; 16.9%; 17.0%; 17.1%; 17.2%; 17.3%; 17.4%; 17.5%; 17.6%; 17.7%; 17.8%; 17.9%; 18.0%; 18.1%; 18.2%; 18.3%; 18.4%; 18.5%; 18.6%; 18.7%; 18.8%; 18.9%; 19.0%; 19.1%; 19.2%; 19.3%; 19.4%; 19.5%; 19.6%; 19.7%; 19.8%; 19.9%; and 20.0%. [00459] TPGS (d-α-tocopheryl polyethylene glycol succinate) penetrant/surfactant - 0.1% to 20%, including: 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; 0.6%; 0.7%; 0.8%; 0.9%; 1.0%; 1.1%; 1.2%; 1.3%; 1.4%; 1.5%; 1.6%; 1.7%; 1.8%; 1.9%; 2.0%; 2.1%; 2.2%; 2.3%; 2.4%; 2.5%; 2.6%; 2.7%; 2.8%; 2.9%; 3.0%; 3.1%; 3.2%; 3.3%; 3.4%; 3.5%; 3.6%; 3.7%; 3.8%; 3.9%; 4.0%; 4.1%; 4.2%; 4.3%; 4.4%; 4.5%; 4.6%; 4.7%; 4.8%; 4.9%; 5.0%; 5.1%; 5.2%; 5.3%; 5.4%; 5.5%; 5.6%; 5.7%; 5.8%; 5.9%; 6.0%; 6.1%; 6.2%; 6.3%; 6.4%; 6.5%; 6.6%; 6.7%; 6.8%; 6.9%; 7.0%; 7.1%; 7.2%; 7.3%; 7.4%; 7.5%; 7.6%; 7.7%; 7.8%; 7.9%; 8.0%; 8.1%; 8.2%; 8.3%; 8.4%; 8.5%; 8.6%; 8.7%; 8.8%; 8.9%; 9.0%; 9.1%; 9.2%; 9.3%; 9.4%; 9.5%; 9.6%; 9.7%; 9.8%; 9.9%; 10.0%; 10.1%; 10.2%; 10.3%; 10.4%; 10.5%; 10.6%; 10.7%; 10.8%; 10.9%; 11.0%; 11.1%; 11.2%; 11.3%; 11.4%; 11.5%; 11.6%; 11.7%; 11.8%; 11.9%; 12.0%; 12.1%; 12.2%; 12.3%; 12.4%; 12.5%; 12.6%; 12.7%; 12.8%; 12.9%; 13.0%; 13.1%; 13.2%; 13.3%; 13.4%; 13.5%; 13.6%; 13.7%; 13.8%; 13.9%; 14.0%; 14.1%; 14.2%; 14.3%; 14.4%; 14.5%; 14.6%; 14.7%; 14.8%; 14.9%; 15.0%; 15.1%; 15.2%; 15.3%; 15.4%; 15.5%; 15.6%; 15.7%; 15.8%; 15.9%; 16.0%; 16.1%; 16.2%; 16.3%; 16.4%; 16.5%; 16.6%; 16.7%; 16.8%; 16.9%; 17.0%; 17.1%; 17.2%; 17.3%; 17.4%; 17.5%; 17.6%; 17.7%; 17.8%; 17.9%; 18.0%; 18.1%; 18.2%; 18.3%; 18.4%; 18.5%; 18.6%; 18.7%; 18.8%; 18.9%; 19.0%; 19.1%; 19.2%; 19.3%; 19.4%; 19.5%; 19.6%; 19.7%; 19.8%; 19.9%; and 20.0%. [00460] SNAC - 0.1% to 80% including; 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; 0.6%; 0.7%; 0.8%; 0.9%; 1.0%; 1.1%; 1.2%; 1.3%; 1.4%; 1.5%; 1.6%; 1.7%; 1.8%; 1.9%; 2.0%; 2.1%; 2.2%; 2.3%; 2.4%; 2.5%; 2.6%; 2.7%; 2.8%; 2.9%; 3.0%; 3.1%; 3.2%; 3.3%; 3.4%; 3.5%; 3.6%; 3.7%; 3.8%; 3.9%; 4.0%; 4.1%; 4.2%; 4.3%; 4.4%; 4.5%; 4.6%; 4.7%; 4.8%; 4.9%; 5.0%; 5.1%; 5.2%; 5.3%; 5.4%; 5.5%; 5.6%; 5.7%; 5.8%; 5.9%; 6.0%; 6.1%; 6.2%; 6.3%; 6.4%; 6.5%; 6.6%; 6.7%; 6.8%; 6.9%; 7.0%; 7.1%; 7.2%; 7.3%; 7.4%; 7.5%; 7.6%; 7.7%; 7.8%; 7.9%; 8.0%; 8.1%; 8.2%; 8.3%; 8.4%; 8.5%; 8.6%; 8.7%; 8.8%; 8.9%; 9.0%; 9.1%; 9.2%; 9.3%; 9.4%; 9.5%; 9.6%; 9.7%; 9.8%; 9.9%; 10.0%; 10.1%; 10.2%; 10.3%; 10.4%; 10.5%; 10.6%; 10.7%; 10.8%; 10.9%; 11.0%; 11.1%; 11.2%; 11.3%; 11.4%; 11.5%; 11.6%; 11.7%; 11.8%; 11.9%; 12.0%; 12.1%; 12.2%; 12.3%; 12.4%; 12.5%; 12.6%; 12.7%; 12.8%; 12.9%; 13.0%; 13.1%; 13.2%; 13.3%; 13.4%; 13.5%; 13.6%; 13.7%; 13.8%; 13.9%; 14.0%; 14.1%; 14.2%; 14.3%; 14.4%; 14.5%; 14.6%; 14.7%; 14.8%; 14.9%; 15.0%; 15.1%; 15.2%; 15.3%; 15.4%; 15.5%; 15.6%; 15.7%; 15.8%; 15.9%; 16.0%; 16.1%; 16.2%; 16.3%; 16.4%; 16.5%; 16.6%; 16.7%; 16.8%; 16.9%; 17.0%; 17.1%; 17.2%; 17.3%; 17.4%; 17.5%; 17.6%; 17.7%; 17.8%; 17.9%; 18.0%; 18.1%; 18.2%; 18.3%; 18.4%; 18.5%; 18.6%; 18.7%; 18.8%; 18.9%; 19.0%; 19.1%; 19.2%; 19.3%; 19.4%; 19.5%; 19.6%; 19.7%; 19.8%; 19.9%; 20.0%; 20.1%; 20.2%; 20.3%; 20.4%; 20.5%; 20.6%; 20.7%; 20.8%; 20.9%; 21.0%; 21.1%; 21.2%; 21.3%; 21.4%; 21.5%; 21.6%; 21.7%; 21.8%; 21.9%; 22.0%; 22.1%; 22.2%; 22.3%; 22.4%; 22.5%; 22.6%; 22.7%; 22.8%; 22.9%; 23.0%; 23.1%; 23.2%; 23.3%; 23.4%; 23.5%; 23.6%; 23.7%; 23.8%; 23.9%; 24.0%; 24.1%; 24.2%; 24.3%; 24.4%; 24.5%; 24.6%; 24.7%; 24.8%; 24.9%; 25.0%; 25.1%; 25.2%; 25.3%; 25.4%; 25.5%; 25.6%; 25.7%; 25.8%; 25.9%; 26.0%; 26.1%; 26.2%; 26.3%; 26.4%; 26.5%; 26.6%; 26.7%; 26.8%; 26.9%; 27.0%; 27.1%; 27.2%; 27.3%; 27.4%; 27.5%; 27.6%; 27.7%; 27.8%; 27.9%; 28.0%; 28.1%; 28.2%; 28.3%; 28.4%; 28.5%; 28.6%; 28.7%; 28.8%; 28.9%; 29.0%; 29.1%; 29.2%; 29.3%; 29.4%; 29.5%; 29.6%; 29.7%; 29.8%; 29.9%; 30.0%; 30.1%; 30.2%; 30.3%; 30.4%; 30.5%; 30.6%; 30.7%; 30.8%; 30.9%; 31.0%; 31.1%; 31.2%; 31.3%; 31.4%; 31.5%; 31.6%; 31.7%; 31.8%; 31.9%; 32.0%; 32.1%; 32.2%; 32.3%; 32.4%; 32.5%; 32.6%; 32.7%; 32.8%; 32.9%; 33.0%; 33.1%; 33.2%; 33.3%; 33.4%; 33.5%; 33.6%; 33.7%; 33.8%; 33.9%; 34.0%; 34.1%; 34.2%; 34.3%; 34.4%; 34.5%; 34.6%; 34.7%; 34.8%; 34.9%; 35.0%; 35.1%; 35.2%; 35.3%; 35.4%; 35.5%; 35.6%; 35.7%; 35.8%; 35.9%; 36.0%; 36.1%; 36.2%; 36.3%; 36.4%; 36.5%; 36.6%; 36.7%; 36.8%; 36.9%; 37.0%; 37.1%; 37.2%; 37.3%; 37.4%; 37.5%; 37.6%; 37.7%; 37.8%; 37.9%; 38.0%; 38.1%; 38.2%; 38.3%; 38.4%; 38.5%; 38.6%; 38.7%; 38.8%; 38.9%; 39.0%; 39.1%; 39.2%; 39.3%; 39.4%; 39.5%; 39.6%; 39.7%; 39.8%; 39.9%; 40.0%; 40.1%; 40.2%; 40.3%; 40.4%; 40.5%; 40.6%; 40.7%; 40.8%; 40.9%; 41.0%; 41.1%; 41.2%; 41.3%; 41.4%; 41.5%; 41.6%; 41.7%; 41.8%; 41.9%; 42.0%; 42.1%; 42.2%; 42.3%; 42.4%; 42.5%; 42.6%; 42.7%; 42.8%; 42.9%; 43.0%; 43.1%; 43.2%; 43.3%; 43.4%; 43.5%; 43.6%; 43.7%; 43.8%; 43.9%; 44.0%; 44.1%; 44.2%; 44.3%; 44.4%; 44.5%; 44.6%; 44.7%; 44.8%; 44.9%; 45.0%; 45.1%; 45.2%; 45.3%; 45.4%; 45.5%; 45.6%; 45.7%; 45.8%; 45.9%; 46.0%; 46.1%; 46.2%; 46.3%; 46.4%; 46.5%; 46.6%; 46.7%; 46.8%; 46.9%; 47.0%; 47.1%; 47.2%; 47.3%; 47.4%; 47.5%; 47.6%; 47.7%; 47.8%; 47.9%; 48.0%; 48.1%; 48.2%; 48.3%; 48.4%; 48.5%; 48.6%; 48.7%; 48.8%; 48.9%; 49.0%; 49.1%; 49.2%; 49.3%; 49.4%; 49.5%; 49.6%; 49.7%; 49.8%; 49.9%; 50.0%; 50.1%; 50.2%; 50.3%; 50.4%; 50.5%; 50.6%; 50.7%; 50.8%; 50.9%; 51.0%; 51.1%; 51.2%; 51.3%; 51.4%; 51.5%; 51.6%; 51.7%; 51.8%; 51.9%; 52.0%; 52.1%; 52.2%; 52.3%; 52.4%; 52.5%; 52.6%; 52.7%; 52.8%; 52.9%; 53.0%; 53.1%; 53.2%; 53.3%; 53.4%; 53.5%; 53.6%; 53.7%; 53.8%; 53.9%; 54.0%; 54.1%; 54.2%; 54.3%; 54.4%; 54.5%; 54.6%; 54.7%; 54.8%; 54.9%; 55.0%; 55.1%; 55.2%; 55.3%; 55.4%; 55.5%; 55.6%; 55.7%; 55.8%; 55.9%; 56.0%; 56.1%; 56.2%; 56.3%; 56.4%; 56.5%; 56.6%; 56.7%; 56.8%; 56.9%; 57.0%; 57.1%; 57.2%; 57.3%; 57.4%; 57.5%; 57.6%; 57.7%; 57.8%; 57.9%; 58.0%; 58.1%; 58.2%; 58.3%; 58.4%; 58.5%; 58.6%; 58.7%; 58.8%; 58.9%; 59.0%; 59.1%; 59.2%; 59.3%; 59.4%; 59.5%; 59.6%; 59.7%; 59.8%; 59.9%; 60.0%; 60.1%; 60.2%; 60.3%; 60.4%; 60.5%; 60.6%; 60.7%; 60.8%; 60.9%; 61.0%; 61.1%; 61.2%; 61.3%; 61.4%; 61.5%; 61.6%; 61.7%; 61.8%; 61.9%; 62.0%; 62.1%; 62.2%; 62.3%; 62.4%; 62.5%; 62.6%; 62.7%; 62.8%; 62.9%; 63.0%; 63.1%; 63.2%; 63.3%; 63.4%; 63.5%; 63.6%; 63.7%; 63.8%; 63.9%; 64.0%; 64.1%; 64.2%; 64.3%; 64.4%; 64.5%; 64.6%; 64.7%; 64.8%; 64.9%; 65.0%; 65.1%; 65.2%; 65.3%; 65.4%; 65.5%; 65.6%; 65.7%; 65.8%; 65.9%; 66.0%; 66.1%; 66.2%; 66.3%; 66.4%; 66.5%; 66.6%; 66.7%; 66.8%; 66.9%; 67.0%; 67.1%; 67.2%; 67.3%; 67.4%; 67.5%; 67.6%; 67.7%; 67.8%; 67.9%; 68.0%; 68.1%; 68.2%; 68.3%; 68.4%; 68.5%; 68.6%; 68.7%; 68.8%; 68.9%; 69.0%; 69.1%; 69.2%; 69.3%; 69.4%; 69.5%; 69.6%; 69.7%; 69.8%; 69.9%; 70.0%; 70.1%; 70.2%; 70.3%; 70.4%; 70.5%; 70.6%; 70.7%; 70.8%; 70.9%; 71.0%; 71.1%; 71.2%; 71.3%; 71.4%; 71.5%; 71.6%; 71.7%; 71.8%; 71.9%; 72.0%; 72.1%; 72.2%; 72.3%; 72.4%; 72.5%; 72.6%; 72.7%; 72.8%; 72.9%; 73.0%; 73.1%; 73.2%; 73.3%; 73.4%; 73.5%; 73.6%; 73.7%; 73.8%; 73.9%; 74.0%; 74.1%; 74.2%; 74.3%; 74.4%; 74.5%; 74.6%; 74.7%; 74.8%; 74.9%; 75.0%; 75.1%; 75.2%; 75.3%; 75.4%; 75.5%; 75.6%; 75.7%; 75.8%; 75.9%; 76.0%; 76.1%; 76.2%; 76.3%; 76.4%; 76.5%; 76.6%; 76.7%; 76.8%; 76.9%; 77.0%; 77.1%; 77.2%; 77.3%; 77.4%; 77.5%; 77.6%; 77.7%; 77.8%; 77.9%; 78.0%; 78.1%; 78.2%; 78.3%; 78.4%; 78.5%; 78.6%; 78.7%; 78.8%; 78.9%; 79.0%; 79.1%; 79.2%; 79.3%; 79.4%; 79.5%; 79.6%; 79.7%; 79.8%; 79.9%; and 80.0%.

Claims

CLAIMS 1. A composition wherein said composition comprises at least one biologically active material selected from the group consisting of: a glucagon-like peptide 1 (GLP-1) agonist; and a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist.

2. The composition of claim 1, wherein the glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of semaglutide; liraglutide; dulaglutide; exenatide; lixisenatide; and a pharmaceutically acceptable salt, analog, homolog or derivative thereof.

3. The composition of any one of the above claims, wherein the sodium glucose co- transporter-2 (SGLT-2) receptor antagonist is selected from the group consisting of dapagliflozin; empagliflozin; ertugliflozin; canagliflozin; bexagliflozin; and a pharmaceutically acceptable salt, analog, homolog or derivative thereof.

4. The composition of any one of the above claims, wherein the composition comprises two biologically active materials selected from the group consisting of: a glucagon-like peptide 1 (GLP-1) agonist; and a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist.

5. The composition of any one of the above claims, wherein the composition is a solid dosage form.

6. The composition of any one of the above claims, wherein the composition is a rapidly disintegrating solid dosage form.

7. The composition of any one of the above claims, wherein the composition is a wafer, tablet or capsule.

8. The composition of any one of the above claims, wherein the composition is a wafer and is neutral pH protected against the acidic pH and enzymatic degradation in the stomach.

9. The composition of any one of the above claims, wherein the biologically active material is present in the composition at a concentration selected from the group consisting of: 0.01% (w/w); 0.1% (w/w); 1% (w/w); 2% (w/w); 3% (w/w); 4% (w/w); 5% (w/w); 6% (w/w); 7% (w/w); 8% (w/w); 9% (w/w); 10% (w/w); 11% (w/w); 12% (w/w); 13% (w/w); 14% (w/w); 15% (w/w); 16% (w/w); 17% (w/w); 18% (w/w); 19% (w/w); 20% (w/w); 21% (w/w); 22% (w/w); 23% (w/w); 24% (w/w); 25% (w/w); 26% (w/w); 27% (w/w); 28% (w/w); 29% (w/w); 30% (w/w); 31% (w/w); 32% (w/w); 33% (w/w); 34% (w/w); 35% (w/w); 36% (w/w); 37% (w/w); 38% (w/w); 39% (w/w); 40% (w/w); 41% (w/w); 42% (w/w); 43% (w/w); 44% (w/w); 45% (w/w); 46% (w/w); 47% (w/w); 48% (w/w); 49% (w/w); 50% (w/w); 0.2-95% (w/w); and 2-95% (w/w); 33-65% (w/w); 4- 55% (w/w); 5-45% (w/w); 6-35% (w/w); 7-25% (w/w); 8-15% (w/w); and within 2 decimal points of each figure.

10. The composition of any one of the above claims, wherein the biologically active material is present in the composition at a quantity selected from the group consisting of: 1ng to 1000mg; 0.01ng to 100mg; 0.01mg; 0.02mg; 0.03mg; 0.04mg; 0.05mg; 0.06mg; 0.07mg; 0.08mg; 0.09mg; 0.10mg; 0.11mg; 0.12mg; 0.13mg; 0.14mg; 0.15mg; 0.16mg; 0.17mg; 0.18mg; 0.19mg; 0.20mg; 0.21mg; 0.22mg; 0.23mg; 0.24mg; 0.25mg; 0.26mg; 0.27mg; 0.28mg; 0.29mg; 0.30mg; 0.31mg; 0.32mg; 0.33mg; 0.34mg; 0.35mg; 0.36mg; 0.37mg; 0.38mg; 0.39mg; 0.40mg; 0.41mg; 0.42mg; 0.43mg; 0.44mg; 0.45mg; 0.46mg; 0.47mg; 0.48mg; 0.49mg; 0.50mg; 0.51mg; 0.52mg; 0.53mg; 0.54mg; 0.55mg; 0.56mg; 0.57mg; 0.58mg; 0.59mg; 0.60mg; 0.61mg; 0.62mg; 0.63mg; 0.64mg; 0.65mg; 0.66mg; 0.67mg; 0.68mg; 0.69mg; 0.70mg; 0.71mg; 0.72mg; 0.73mg; 0.74mg; 0.75mg; 0.76mg; 0.77mg; 0.78mg; 0.79mg; 0.80mg; 0.81mg; 0.82mg; 0.83mg; 0.84mg; 0.85mg; 0.86mg; 0.87mg; 0.88mg; 0.89mg; 0.90mg; 0.91mg; 0.92mg; 0.93mg; 0.94mg; 0.95mg; 0.96mg; 0.97mg; 0.98mg; 0.99mg; 1.00mg; 0.1mg; 0.2mg; 0.3mg; 0.4mg; 0.5mg; 0.6mg; 0.7mg; 0.8mg; 0.9mg; 1.0mg; 1mg; 2mg; 3mg; 4mg; 5mg; 6mg; 7mg; 8mg; 9mg; 10mg; 11mg; 12mg; 13mg; 14mg; 15mg; 16mg; 17mg; 18mg; 19mg; 20mg; 21mg; 22mg; 23mg; 24mg; 25mg; 26mg; 27mg; 28mg; 29mg; 30mg; 31mg; 32mg; 33mg; 34mg; 35mg; 36mg; 37mg; 38mg; 39mg; 40mg; 41mg; 42mg; 43mg; 44mg; 45mg; 46mg; 47mg; 48mg; 49mg; 50mg; 51mg; 52mg; 53mg; 54mg; 55mg; 56mg; 57mg; 58mg; 59mg; 60mg; 61mg; 62mg; 63mg; 64mg; 65mg; 66mg; 67mg; 68mg; 69mg; 70mg; 71mg; 72mg; 73mg; 74mg; 75mg; 76mg; 77mg; 78mg; 79mg; 80mg; 81mg; 82mg; 83mg; 84mg; 85mg; 86mg; 87mg; 88mg; 89mg; 90mg; 91mg; 92mg; 93mg; 94mg; 95mg; 96mg; 97mg; 98mg; 99mg; 100mg; 101mg; 102mg; 103mg; 104mg; 105mg; 106mg; 107mg; 108mg; 109mg; 110mg; 111mg; 112mg; 113mg; 114mg; 115mg; 116mg; 117mg; 118mg; 119mg; 120mg; 121mg; 122mg; 123mg; 124mg; 125mg; 126mg; 127mg; 128mg; 129mg; 130mg; 131mg; 132mg; 133mg; 134mg; 135mg; 136mg; 137mg; 138mg; 139mg; 140mg; 141mg; 142mg; 143mg; 144mg; 145mg; 146mg; 147mg; 148mg; 149mg; 150mg; 151mg; 152mg; 153mg; 154mg; 155mg; 156mg; 157mg; 158mg; 159mg; 160mg; 161mg; 162mg; 163mg; 164mg; 165mg; 166mg; 167mg; 168mg; 169mg; 170mg; 171mg; 172mg; 173mg; 174mg; 175mg; 176mg; 177mg; 178mg; 179mg; 180mg; 181mg; 182mg; 183mg; 184mg; 185mg; 186mg; 187mg; 188mg; 189mg; 190mg; 191mg; 192mg; 193mg; 194mg; 195mg; 196mg; 197mg; 198mg; 199mg; 200mg; 0.01mg to 1mg; 0.1mg to 1mg; 1 to 200mg; 1 to 100mg; 1 to 50mg; 1 to 25mg; 1 to 15mg; 1 to 10mg; 10 to 100mg; 10 to 75mg; 10mg to 50mg; and 10mg to 25mg.

11. The composition of any one of the above claims, wherein the biologically active material is present in the composition at a quantity selected from the group consisting of: 0.01mg; 0.1mg; 1mg; 2mg; 5mg; 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg.

12. The composition of any one of the above claims, wherein the biologically active material is present in the composition at a quantity selected from the group consisting of: semaglutide 15mg; liraglutide 21mg; dulaglutide 10mg; exenatide 2mg; and lixisenatide 20mg.

13. The composition of any one of the above claims, wherein the biologically active material is present in the composition at a quantity selected from the group consisting of: dapagliflozin 10mg; empagliflozin 25mg; and ertugliflozin 5mg.

14. The composition of any one of the above claims, wherein the composition comprises one or more agents selected from the group consisting of: an entero-hepatic recycling agent; an absorption agent; a bile salt; a penetrant; a surfactant; an ionic water soluble post-disintegration viscosity agent; a mucolytic (mucus buster); a mucoadhesive; an adjuvant; a disintegration viscosity agent; a permeation enhancer; an absorption enhancer; and a entero-hepatic-biliary recirculation agent.

15. The composition of any one of the above claims, wherein the entero-hepatic recycling agent is selected from the group consisting of: glycodeoxycholate; glycocholate; taurocholate; glycolithocholate; glycohyocholate; tauroursodeoxycholate; taurohyodeoxycholate; and salts thereof.

16. The composition of any one of the above claims, wherein the composition comprises a plurality of entero-hepatic recycling agents.

17. The composition of any one of the above claims, wherein the entero-hepatic recycling agent is selected from the group consisting of: sodium glycodeoxycholate; and sodium deoxycholate.

18. The composition of any one of the above claims, wherein the concentration of the entero-hepatic recycling agent is selected from the group consisting of: 0.01%; 0.5%; 1%; 0.5%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; and within 2 decimal points of each figure (w/w).

19. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) are bile salts and soy lecithin.

20. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) are permeation enhancers.

21. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) open tight junctions in the sublingual/gastro-intestinal mucosa cells.

22. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) influence the integrity of tight junctions between epithelial cells and modulate these tight junctions, allowing for an increased in paracellular transport.

23. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) improve/enhance the absorption of lipophilic compounds as they can interact with both lipophilic drugs and the lipids present in cell membranes

24. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) and the glucagon-like peptide 1 (GLP-1) agonist form a complex.

25. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) and the glucagon-like peptide 1 (GLP-1) agonist form a complex which has a particle size less than 2000nm.

26. The composition of any one of the above claims, wherein the entero-hepatic recycling agent(s) and the glucagon-like peptide 1 (GLP-1) agonist form a complex which is absorbed into the blood circulation and metabolised into the active glucagon-like peptide 1 (GLP-1) agonist improving the bioavailability of the glucagon-like peptide 1 (GLP-1) agonist.

27. The composition of any one of the above claims, wherein the ionic water soluble post- disintegration viscosity agent is selected from the group consisting of: carboxymethyl cellulose; anionic substituted cellulose or starch derivatives, such as salts of carboxymethyl celluloses (CMC), alginate and starch glycolates.

28. The composition of any one of the above claims, wherein the ionic water soluble post- disintegration viscosity agent is carboxymethyl cellulose.

29. The composition of any one of the above claims, wherein the ionic water soluble post- disintegration viscosity agent is at a concentration selected from the group consisting of: 1%; 0.5%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; and within 2 decimal points of each figure (w/w).

30. The composition of any one of the above claims, wherein the disintegration viscosity agent is sodium alginate.

31. The composition of any one of the above claims, wherein the disintegration viscosity agent is at a concentration selected from the group consisting of: 1%; 0.5%-10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; and within 2 decimal points of each figure (w/w).

32. The composition of any one of the above claims, wherein the permeation enhancer is SNAC (salcaprozate sodium) or a non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate).

33. The composition of any one of the above claims, wherein the permeation enhancer is SNAC (salcaprozate sodium) and is surfactant-like structurally and has the ability to chaperone poorly-permeable macromolecules across plasma membranes via a transcellular mode of action and helps sublingual absorption of peptides.

34. The composition of any one of the above claims, wherein the SNAC (salcaprozate sodium) and the glucagon-like peptide 1 (GLP-1) agonist form a complex; or wherein the non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) and the glucagon-like peptide 1 (GLP-1) form a complex.

35. The composition of any one of the above claims, wherein the permeation enhancer is at a concentration selected from the group consisting of: 0%; 0.05%-10%; 0.5%; 1%- 10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%, 30%, 40%; and within 2 decimal points of each figure (w/w).

36. The composition of any one of the above claims, wherein the permeation enhancer is at a quantity selected from the group consisting of: 0mg; 5mg; 10mg; 25mg; 30mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg.

37. The composition of any one of the above claims, wherein the permeation enhancer protects the glucagon-like peptide 1 (GLP-1) agonist against the effects of pepsin (primary digestive enzymes in the stomach which digest/convert protein and peptides to amino acids).

38. The composition of any one of the above claims, wherein the composition comprises a glucagon-like peptide 1 (GLP-1) agonist-cholate- non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate)s-sodium glucose co-transporter-2 (SGLT-2) receptor antagonist cluster or glucagon-like peptide 1 (GLP-1) agonist-cholate-non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate)-sodium glucose co-transporter-2 (SGLT- 2) receptor antagonist cluster.

39. The composition of any one of the above claims, wherein the composition comprises a semaglutide-cholate-SNAC-dapagliflozin cluster or semaglutide-cholate-non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate)-dapagliflozin cluster

40. The composition of any one of the above claims, wherein the composition is formulated to pH 5-8.0 to inhibit pepsin activity.

41. The composition of any one of the above claims, wherein the entero-hepatic-biliary recirculation agent is soy lecithin.

42. The composition of any one of the above claims, wherein the permeation enhancer is SNAC or non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate).

43. The composition of any one of the above claims, wherein the entero-hepatic-biliary recirculation agent is at a concentration selected from the group consisting of: 0.05%- 10%; 0.5%; 1%-10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 20%, 30%, 40%; and within 2 decimal points of each figure (w/w).

44. The composition of any one of the above claims, wherein the entero-hepatic-biliary recirculation agent is at a quantity selected from the group consisting of: 5mg; 10mg; 25mg; 30mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg.

45. The composition of any one of the above claims, wherein the entero-hepatic-biliary recirculation agent provides absorption enhancement.

46. The composition of any one of the above claims, wherein the entero-hepatic-biliary recirculation agent provides absorption enhancement using factors selected from the group consisting of: a local alteration in the membrane structure and modification of its permeability; bioadhesion to the mucosa surfaces; and the lowering of the mucociliary clearance.

47. The composition of any one of the above claims, wherein the composition comprises a mucoadhesive polymer, with a mucolytic property to break the GI/oro-mucosal mucus layer/barrier for bioactive penetration.

48. The composition of any one of the above claims, wherein the composition comprises one or more agents selected from the group consisting of; sodium glycodeoxycholate; sodium deoxycholate; carboxymethyl cellulose; sodium alginate; SNAC (salcaprozate sodium); a non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate); and soy lecithin.

49. The composition of any one of the above claims, wherein the composition comprises one or more biologically active materials and agents selected from Table 1 or Table 2.

50. The composition of any one of the above claims, wherein the composition has a pH selected from the group consisting of: between 5 to 6; between 4 to 7.5; between 6 to 7.5; between 7.0 – 7.5; and between 7.0 – 8.0.

51. The composition of any one of the above claims, wherein the composition is a solid.

52. The composition of any one of the above claims, wherein the composition is lyophilised.

53. The composition of any one of the above claims, wherein the particles of the composition have a size no greater than 2000 nm.

54. The composition of any one of the above claims, wherein the particles of the composition have a nanoparticulate size.

55. The composition of any one of the above claims, wherein the composition comprises further pharmaceutically acceptable additives and agents.

56. The composition of any one of the above claims, wherein the composition comprises a pharmaceutically acceptable buffering reagent.

57. The composition of any one of the above claims, wherein the buffering reagent is selected from the group consisting of: salts of phosphates, carbonates, Tris; preferably combinations of phosphate salts; including sodium carbonate.

58. The composition of any one of the above claims, wherein the buffering reagent is present at a concentration selected from the group consisting of: 0.1-0.5%; 0.1%; 0.2%; 0.3%; 0.4%; 0.5%; and within 2 decimal points of each figure (w/w).

59. The composition of any one of the above claims, wherein the wafers are buffered with a suitable buffer, most preferably a blend of mono- and di-alkaline salt phosphates, adjusted to afford a pH optimal for the stability of the chosen biological active, generally between 4 and 8.0.

60. The composition of any one of the above claims, wherein the composition comprises a colouring agent.

61. The composition of any one of the above claims, wherein the composition comprises a flavouring agent.

62. The composition of any one of the above claims, wherein the composition comprises a stability agent.

63. The composition of any one of the above claims, wherein the stability agent is selected from the group consisting of: metal chelators such as EDTA, pharmaceutically acceptable surfactant including polysorbate 80.

64. The composition of any one of the above claims, wherein the composition is a glucagon-like peptide 1 (GLP-1) agonist bile salt-lecithin complex.

65. The composition of any one of the above claims, wherein the composition is a glucagon-like peptide 1 (GLP-1) agonist bile salt-lecithin-SNAC (salcaprozate sodium) complex or glucagon-like peptide 1 (GLP-1) agonist bile salt-lecithin-non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate)- complex

66. The composition of any one of the above claims, wherein the composition comprises a complex selected from the group consisting of: glucagon-like peptide 1 (GLP-1) agonist - bile salt - lecithin - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) complex; glucagon-like peptide 1 (GLP-1) agonist - bile salt – lecithin - SNAC (salcaprozate sodium) complex; glucagon-like peptide 1 (GLP-1) agonist - entero-hepatic recycling agent(s) - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) complex; glucagon-like peptide 1 (GLP-1) agonist - SNAC (salcaprozate sodium) complex; glucagon-like peptide 1 (GLP-1) agonist - entero-hepatic recycling agent(s) - SNAC (salcaprozate sodium) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - SNAC (salcaprozate sodium) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - SNAC (salcaprozate sodium) complex; a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - SNAC (salcaprozate sodium) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - bile salt – lecithin - SNAC (salcaprozate sodium) complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - non-ionic ester alkoxylate (or alkanoic acid ester alkoxylate)complex; glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - SNAC (salcaprozate sodium) complex; and glucagon-like peptide 1 (GLP-1) agonist - a sodium glucose co-transporter-2 (SGLT-2) receptor antagonist - entero-hepatic recycling agent(s) - SNAC (salcaprozate sodium) complex.

67. The composition of any one of the above claims, wherein the composition disintegrates once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s (seconds).

68. The composition of any one of the above claims, wherein the composition disintegrates once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s; <130s; <140s; <150s; <160s; <170s; <180s; <190s; <200s; <210s; <220s; <230s; <240s; <250s; <260s; <270s; <280s; <290s; <300s; <310s; <320s; <330s; <340s; <350s; <360s; <370s; <380s; <390s; <400s; <410s; <420s; <430s; <440s; <450s; <460s; <470s; <480s; <490s; <500s; <510s; <520s; <530s; <540s; <550s; <560s; <570s; <580s; <590s; <600s; <610s; <620s; <630s; <640s; <650s; <660s; <670s; <680s; <690s; <700s; <710s; <720s; <730s; <740s; <750s; <760s; <770s; <780s; <790s; <800s; <810s; <820s; <830s; <840s; <850s; <860s; <870s; <880s; <890s; <900s; <900s; <930s; <960s; <990s; <1020s; <1050s; <1080s; <1110s; <1140s; <1170s; <1200s; <1230s; <1260s; <1290s; <1320s; <1350s; <1380s; <1410s; <1440s; <1470s; <1500s; <1530s; <1560s; <1590s; <1620s; <1650s; <1680s; <1710s; <1740s; <1770s; <1800s; <1830s; <1860s; <1890s; <1920s; <1950s; <1980s; <2010s; <2040s; <2070s; <2100s; <2130s; <2160s; <2190s; <2220s; <2250s; <2280s; <2310s; <2340s; <2370s; <2400s; <2430s; <2460s; <2490s; <2520s; <2550s; <2580s; <2610s; <2640s; <2670s; <2700s; <2730s; <2760s; <2790s; <2820s; <2850s; <2880s; <2910s; <2940s; <2970s; <3000s; <3030s; <3060s; <3090s; <3120s; <3150s; <3180s; <3210s; <3240s; <3270s; <3300s; <3330s; <3360s; <3390s; <3420s; <3450s; <3480s; <3510s; <3540s; <3570s; <3600s; <3630s; <3660s; <3690s; <3720s; <3750s; <3780s; <3810s; <3840s; <3870s; <3900s; <3930s; <3960s; <3990s; <4020s; <4050s; <4080s; <4110s; <4140s; <4170s; <4200s; and <4230s (seconds).

69. The composition of any one of the above claims, wherein the composition disintegrates in the oral cavity without leaving a residue of said dosage form in the oral cavity that is detectable by a subject, thereby avoiding the urge for the subject to swallow the composition.

70. The composition of any one of the above claims, wherein the composition dissolves once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s; 180s, preferably 15-60s (seconds).

71. The composition of any one of the above claims, wherein the composition dissolves once placed in the oral cavity in a time period selected from the group consisting of: <10s; <20s; <30s; <40s; <50s; <60s; <70s; <80s; <90s; <100s; <110s; <120s; <130s; <140s; <150s; <160s; <170s; <180s; <190s; <200s; <210s; <220s; <230s; <240s; <250s; <260s; <270s; <280s; <290s; <300s; <310s; <320s; <330s; <340s; <350s; <360s; <370s; <380s; <390s; <400s; <410s; <420s; <430s; <440s; <450s; <460s; <470s; <480s; <490s; <500s; <510s; <520s; <530s; <540s; <550s; <560s; <570s; <580s; <590s; <600s; <610s; <620s; <630s; <640s; <650s; <660s; <670s; <680s; <690s; <700s; <710s; <720s; <730s; <740s; <750s; <760s; <770s; <780s; <790s; <800s; <810s; <820s; <830s; <840s; <850s; <860s; <870s; <880s; <890s; <900s; <900s; <930s; <960s; <990s; <1020s; <1050s; <1080s; <1110s; <1140s; <1170s; <1200s; <1230s; <1260s; <1290s; <1320s; <1350s; <1380s; <1410s; <1440s; <1470s; <1500s; <1530s; <1560s; <1590s; <1620s; <1650s; <1680s; <1710s; <1740s; <1770s; <1800s; <1830s; <1860s; <1890s; <1920s; <1950s; <1980s; <2010s; <2040s; <2070s; <2100s; <2130s; <2160s; <2190s; <2220s; <2250s; <2280s; <2310s; <2340s; <2370s; <2400s; <2430s; <2460s; <2490s; <2520s; <2550s; <2580s; <2610s; <2640s; <2670s; <2700s; <2730s; <2760s; <2790s; <2820s; <2850s; <2880s; <2910s; <2940s; <2970s; <3000s; <3030s; <3060s; <3090s; <3120s; <3150s; <3180s; <3210s; <3240s; <3270s; <3300s; <3330s; <3360s; <3390s; <3420s; <3450s; <3480s; <3510s; <3540s; <3570s; <3600s; <3630s; <3660s; <3690s; <3720s; <3750s; <3780s; <3810s; <3840s; <3870s; <3900s; <3930s; <3960s; <3990s; <4020s; <4050s; <4080s; <4110s; <4140s; <4170s; <4200s; and <4230s (seconds).

72. The composition of any one of the above claims, wherein the composition dissolves in the oral cavity without leaving a residue of said dosage form in the oral cavity that is detectable by a subject, thereby avoiding the urge for the subject to swallow the composition.

73. The composition of any one of the above claims, wherein water is removed from the combined agents by a freeze-drying process to a residual level of 0-10%, preferably 0- 5%, most preferably 3-5%.

74. The composition of any one of the above claims, wherein the composition has a porosity profile selected from the group consisting of: the proportion of water removed by lyophilization is 65-75%; and the proportion of water removed by lyophilization is >60%.

75. The composition of any one of the above claims, wherein the composition has undergoing weight loss selected from the group consisting of: between 0.01% and 0.1%; between 0.01% and 1%; between 0. 1% and 1%; between 0.01% and 0.1%; between 1 and 30%; between 5 and 25%; between 8 and 20%; 0.01%; 0.1%; 1%: 2%: 3%: 4%: 5%: 6%: 7%: 8%: 9%: 10%: 11%: 12%: 13%: 14%: 15%: 16%: 17%: 18%: 19%: 20%: 21%: 22%: 23%: 24%: 25%: 26%: 27%: 28%: 29%: 30% and within 2 decimal points of each figure.

76. The composition of any one of the above claims, wherein the composition has a residual moisture content after lyophilisation selected from the group consisting of: between: 0.01 and 20%; between 0.1 and 10%; between 1 and 5%; 0.01%; 0.02%; 0.03%; 0.04%; 0.05%; 0.06%; 0.07%; 0.08%; 0.09%; 0.10%; 0.01%; 0.02%; 0.03%; 0.04%; 0.05%; 0.06%; 0.07%; 0.08%; 0.09%; 0.10%; 1%; 2%; 3%; 4%; 5%; 6%; 7%; 8%; 9%; 10%; 11%; 12%; 13%; 14%; 15%; 16%; 17%; 18%; 19%; 20% and within 2 decimal points of each figure.

77. The composition of any one of the above claims, wherein the composition is stable for a time period selected from the group consisting of: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; 7 weeks; 8 weeks; 9 weeks; 10 weeks; 11 weeks; 12 weeks; 13 weeks; 14 weeks; 15 weeks; 16 weeks; 17 weeks; 18 weeks; 19 weeks; 20 weeks; 21 weeks; 22 weeks; 23 weeks; 24 weeks; 25 weeks; 26 weeks; 27 weeks; 28 weeks; 29 weeks; 30 weeks; 31 weeks; 32 weeks; 33 weeks; 34 weeks; 35 weeks; 36 weeks; 37 weeks; 38 weeks; 39 weeks; 40 weeks; 41 weeks; 42 weeks; 43 weeks; 44 weeks; 45 weeks; 46 weeks; 47 weeks; 48 weeks; 49 weeks; 50 weeks; 51 weeks; 52 weeks; 1 month; 2 months; 3 months; 4 months; 5 months; 6 months; 7 months; 8 months; 9 months; 10 months; 11 months; 12 months; 13 months; 14 months; 15 months; 16 months; 17 months; 18 months; 19 months; 20 months; 21 months; 22 months; 23 months; 24 months; 25 months; 26 months; 27 months; 28 months; 29 months; 30 months; 31 months; 32 months; 33 months; 34 months; 35 months; 36 months; 37 months; 38 months; 39 months; 40 months; 41 months; 42 months; 43 months; 44 months; 45 months; 46 months; 47 months; 48 months; 49 months; 50 months; 51 months; 52 months; 53 months; 54 months; 55 months; 56 months; 57 months; 58 months; 59 months; 60 months; 1 month to 12 months; 12 months to 24 months; 12 months to 36 months; 12 months to 48 months; 1 year to 2 years; 1 year to 3 years; and 1 year to 5 years. The composition of any one of the above claims, wherein the composition is stable as demonstrated by a potency assay run against a reference biological active material.

78. A pharmaceutical composition comprising the composition of any one of claims 1 to 77 together with a pharmaceutical excipient or carrier.

79. A dosage form comprising the composition of any one of claims 1 to 77.

80. The dosage form of claim 79, wherein the dosage form comprises the biologically active material at a dose selected from the group consisting of: 2mg; 5mg 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; and 10 to 50mg.

81. The dosage form of any one of claims 79 to 80, wherein the dosage form comprises the biologically active material at a dose selected from the group consisting of: semaglutide 15mg; liraglutide 21mg; dulaglutide 10mg; exenatide 2mg; and lixisenatide 20mg.

82. The dosage form of any one of claims 79 to 81, wherein the dosage form comprises the biologically active material at a dose selected from the group consisting of: dapagliflozin 10mg; empagliflozin 25mg; and ertugliflozin 5mg.

83. The dosage form of any one of claims 79 to 82, wherein the dosage form is solid.

84. The dosage form of any one of claims 79 to 83, wherein the dosage form is freeze dried.

85. The dosage form of any one of claims 79 to 84, wherein the dosage form is a wafer.

86. A method of treating or preventing or delaying a disease or disorder, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of claims 79 to 85.

87. The method of claim 86, wherein the disease or disorder is selected from the group consisting of: appetite suppression; weight loss; weight management; obesity; type 2 diabetes, regulate blood sugar; lower the risk of heart attack, stroke, or death in patients with type 2 diabetes and heart or blood vessel disease; cardiovascular disease; Alzheimer's disease; nonalcoholic steatohepatitis (NASH).

88. The method of any one of claims 86 to 87, wherein the dosage form is administered to deliver a therapeutic effective amount of the biological active material.

89. The method of any one of claims 86 to 88, wherein the therapeutically effective amount is administered to the subject utilising a dosing regimen selected from the group consisting of: twice hourly; hourly; once every six hours; once every 8 hours; once every 12 hours; once daily; twice weekly; once weekly; once every 2 weeks; once every 6 weeks; once a month; once every 2 months; once every 3 months; once every 4 months; once every 5 months; once every 6 months; once yearly; and once.

90. The method of any one of claims 86 to 89, wherein the dosage form delivers a therapeutic effective amount of the biologically active material.

91. The method of any one of claims 86 to 90, wherein the therapeutically effective amount is an amount of biologically active material selected from the group consisting of: between 0.001 to 100mg/kg; between 2 and 50mg/kg; between 5 and 40mg/kg; between 10 and 30mg/kg; between 20 and 25mg/kg; and 20mg/kg/day.

92. The method of any one of claims 86 to 91, wherein the therapeutically effective amount is an amount of biologically active material selected from the group consisting of: 2mg; 5mg 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; 10 to 50mg per dosage event.

93. The method of any one of claims 86 to 92, wherein the therapeutically effective amount is an amount of biologically active material selected from the group consisting of: 2mg; 5mg 10mg; 15mg; 20mg; 21mg; 0.25mg to 100mg; 1mg to 25mg; 1 mg to 50 mg; 1 mg to 30mg; 2 to 30mg; 5 mg to 15mg; 10mg to 20mg; 10 to 50mg per day.

94. The method of any one of claims 86 to 93, wherein the therapeutically effective amount is administered to the subject using a method selected from the group consisting of: orally; sublingually; buccally.

95. The method of any one of claims 86 to 94, wherein the therapeutically effective amount is administered to the subject using a method selected from the group consisting of: beneath the tongue or buccally.

96. The method of any one of claims 86 to 95, wherein detectable levels of the biologically active material enters the circulation system.

97. The method of any one of claims 86 to 96, wherein the detectable levels of the biologically active material that enters the circulation system is selected from the group consisting of: less than 0.001%; less than 0.01%; less than 0.1%; less than 2%; less than 3%; less than 4%; less than 5%; less than 6%; less than 7%; less than 8%; less than 9%; less than 10%; less than 11%; less than 12%; less than 13%; less than 14%; less than 15%; less than 16%; less than 17%; less than 18%; less than 19%; less than 20%; less than 21%; less than 22%; less than 23%; less than 24%; ess than 25%; less than 26%; less than 27%; less than 28%; less than 29%; less than 30%; less than 31%; less than 32%; less than 33%; less than 34%; less than 35%; less than 36%; less than 37%; less than 38%; less than 39%; less than 40%; less than 41%; less than 42%; less than 43%; less than 44%; less than 45%; less than 46%; less than 47%; less than 48%; less than 49%; less than 50%; less than 51%; less than 52%; less than 53%; less than 54%; less than 55%; less than 56%; less than 57%; less than 58%; less than 59%; less than 60%; less than 61%; less than 62%; less than 63%; less than 64%; less than 65%; less than 66%; less than 67%; less than 68%; less than 69%; less than 70%; less than 71%; less than 72%; less than 73%; less than 74%; and less than 75% (w/w%).

98. The method of any one of claims 86 to 97, wherein said biologically active material is absorbed by diffusion directly into the systemic circulation.

99. The method of any one of claims 86 to 98, wherein said biologically active material is sublingually absorbed rapidly.

100. The method of any one of claims 86 to 99, wherein the drug form is delivered sublingually and more suitable for patients phobic to subcutaneous injection.

101. The method of any one of claims 86 to 100, wherein the sublingual administered glucagon-like peptide 1 (GLP-1) agonist has multiple sites action, that is, initial rapid sublingual absorption, then, those glucagon-like peptide 1 (GLP-1) agonists not absorbed sublingually is swallowed into the stomach which then undergo stomach absorption and finally reaching the small intestine which then react locally in the intestinal and colon mucosa L-cells (enteroendocrine cells which produce and release hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)), a local intrinsic reaction for immediate satiety effect.

102. The method of any one of claims 86 to 101, wherein the released GLP-1 stimulates pancreatic insulin, which helps regulate blood sugar levels and also inhibit glucagon secretion, slowing down gastric emptying, and promote a feeling of satiety or fullness (appetite suppression).

103. The method of any one of claims 86 to 102, wherein the released PYY hormone produced by L-cells helps to reduce appetite, slow down gut motility, and modulate the absorption of nutrients from the intestines.

104. The method of any one of claims 86 to 103, wherein the glucagon-like peptide 1 (GLP- 1) agonist -bile salt-lecithin complex undergoes absorption in the small intestine and the absorbed complex undergoes liver first-pass metabolism and the free glucagon- like peptide 1 (GLP-1) agonist secrets back into the small intestine (entero-hepatic recirculation) actively attached onto the L-cells again releasing GLP-1 and PYY resulting in their pharmacological satiety effect, and wherein the parenteral administered semaglutide only has a systemic effect with minimal or no local intestinal/colon mucosa effect.

105. The method of any one of claims 86 to 104, wherein currently oral semaglutide has very low oral bioavailability (0.8 to 1.4%) and may need up to 50 mg per dose to be effective, yet this sublingual semaglutide uses 3 times (15mg versus 50mg) less semaglutide due to its multiple sites of action.

106. The method of any one of claims 86 to 105, wherein there is a correlation between semaglutide tablet erosion and semaglutide plasma exposure and wherein full tablet erosion at 1 hour resulted in very low plasma exposure of semaglutide, whereas less than 54 % tablet erosion resulted in high plasma exposure of semaglutide, hence the mandatory criteria of using less than 120mL of water during oral administration and wherein there is no problem with sublingual administration (no water needed for disintegration, fully disintegrated with saliva).

107. The method of any one of claims 86 to 106, wherein the t½ of the administered glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of: between 15 and 20 min; between 20 and 25 min; between 25 and 30 min; between 30 and 35 min; between 35 and 40 min; between 40 and 45 min; between 45 and 50 min; between 30 and 60 min; between 1 and 2 hrs; between 2 and 3 hrs; between 3 and 4 hrs; between 4 and 5 hrs; between 5 and 6 hrs; between 6 and 12 hrs; between 12 and 24 hrs; between 1 and 2 days; between 2 and 3 days; between 3 and 4 days; between 4 and 5 days; between 5 and 6 days; between 6 and 7 days; between 6 and 7 days; between 1 and 2 weeks; between 2 and 3 weeks; between 3 and 4 weeks; between 1 and 2 months; between 2 and 3 months; between 3 and 4 months; between 4 and 5 months; between 5 and 6 months; between 6 and 12 months; and between 1 and 2 years.

108. The method of any one of claims 86 to 107, wherein the t½ of the administered glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of: between 30 and 40 min.

109. The method of any one of claims 86 to 108, wherein the t½ of the administered glucagon-like peptide 1 (GLP-1) agonist is selected from the group consisting of: 33 min; 34 min; 35 min; 36 min; 38 min; between 30 and 40 min.

110. The method of any one of claims 86 to 109, wherein the t½ of the administered semaglutide is selected from the group consisting of: 33 min; 34 min; 35 min; 36 min; 38 min; between 30 and 40 min.

111. A method of appetite suppression, weight loss and/or weight management, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of claims 79 to 85.

112. Use of the composition of claims 1 to 77 in the manufacture of a medicament for the treatment or prevention of a disease or disorder.

113. A process of preparing the composition of claims 1 to 77, said process comprising the steps of: (1) combining at least one matrix forming agent with a biological active material to form a mixture; and (2) freeze drying the mixture to form the solid dosage form.

114. A kit comprising the dosage form of claims 79 to 85 together with instructions for its use.

115. The kit of claim 114, wherein the kit is directed to treating of preventing a disease or disorder selected from the group consisting of: appetite suppression; weight loss; weight management; obesity; type 2 diabetes, regulate blood sugar; lower the risk of heart attack, stroke, or death in patients with type 2 diabetes and heart or blood vessel disease; cardiovascular disease; Alzheimer's disease; nonalcoholic steatohepatitis (NASH).