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WO2025153822A1 - Formulations de poudre de 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt) - Google Patents

Formulations de poudre de 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt)

Info

Publication number
WO2025153822A1
WO2025153822A1 PCT/GB2025/050076 GB2025050076W WO2025153822A1 WO 2025153822 A1 WO2025153822 A1 WO 2025153822A1 GB 2025050076 W GB2025050076 W GB 2025050076W WO 2025153822 A1 WO2025153822 A1 WO 2025153822A1
Authority
WO
WIPO (PCT)
Prior art keywords
dmt
meo
formulation
hpmc
dry powder
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/GB2025/050076
Other languages
English (en)
Inventor
Jason Gray
Karina WOJDAT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beckley Psytech Ltd
Original Assignee
Beckley Psytech Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB2400703.1A external-priority patent/GB202400703D0/en
Priority claimed from US18/607,093 external-priority patent/US12246005B2/en
Application filed by Beckley Psytech Ltd filed Critical Beckley Psytech Ltd
Publication of WO2025153822A1 publication Critical patent/WO2025153822A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin

Definitions

  • 5-Methoxy-N,N-Dimethyltryptamine (-MeO-DMT) Formulations FIELD OF THE INVENTION
  • This invention relates to 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) formulations, more particularly intranasal formulations of pharmaceutically acceptable salts of 5-MeO-DMT, nasal delivery devices comprising the same, and methods of administration and treatment.
  • 5-methoxy-N,N-dimethyltryptamine is a pharmacologically active compound of the tryptamine class and has the chemical formula:
  • 5-MeO-DMT is a psychoactive/psychedelic substance found in nature.
  • an active nasal delivery device comprising a pharmaceutical formulation of 5- MeO-DMT and one or more pharmaceutically acceptable carriers or excipients.
  • the pharmaceutical formulation of 5-MeO-DMT is a spray dried formulation.
  • the low viscosity HPMC has a viscosity less than about 20, 15, 10, 5, 1 mPa•s, optionally where the HPMC is a HPMC containing about 7.0-12.0% (e.g., 7% ⁇ 1%, 8% ⁇ 1%, 9% ⁇ 1%, 10% ⁇ 1%, 11% ⁇ 1%, or 12% ⁇ 1%) hydroxypropyl content, about 28.0-30.0% (e.g., 28% ⁇ 2%, 29% ⁇ 2%, or 30% ⁇ 2%) methoxy content, and a viscosity of about 4.8-7.2 (e.g., 4.8 ⁇ 0.5, 5.3 ⁇ 0.5, 5.7 ⁇ 0.5, 6.2 ⁇ 0.5, 6.7 ⁇ 0.5, 7 ⁇ 0.5, or 7.2 ⁇ 0.5) mPa•s.
  • 4.8-7.2 e.g., 4.8 ⁇ 0.5, 5.3 ⁇ 0.5, 5.7 ⁇ 0.5, 6.2 ⁇ 0.5, 6.7 ⁇ 0.5, 7 ⁇ 0.5, or 7.2 ⁇ 0.5
  • the formulation comprises a polyol.
  • the polyol may be mannitol, xylitol, sorbitol, maltitol, erythritol, lactitol or isomalt, further optionally the polyol is sorbitol.
  • the formulation comprises a 5-MeO-DMT salt.
  • the formulation comprises 5- MeO-DMT benzoate.
  • the formulation comprises 5-MeO-DMT hydrochloride.
  • the formulation comprises 5-MeO-DMT hydrobromide.
  • the 5-MeO-DMT salt is amorphous. In an embodiment, the 5-MeO-DMT salt is crystalline.
  • the active nasal delivery device comprises: a dispenser outlet; an air expeller for generating a flow of air while the device is being actuated; and at least one reservoir that contains a single dose of formulation.
  • the active nasal delivery device comprises: a dispenser outlet; an air expeller for generating a flow of air while the device is being actuated, said air expeller including a piston that slides in an air chamber between a rest position and a dispensing position, said air chamber including a cylindrical body in which said piston slides in airtight manner; and at least one reservoir that contains a single dose of formulation, said reservoir including an air inlet that is connected to said air expeller, and a formulation outlet that is connected to said dispenser outlet, said air inlet including a formulation retainer member for retaining the formulation in the reservoir until the formulation is dispensed, and said formulation outlet being closed by a closure element that is force fitted in the formulation outlet of the reservoir; said device further including a mechanical opening system that co-operates with said closure element so as to expel said closure element mechanical
  • a state-stable amorphous dry powder formulation comprising 5-MeO-DMT HBr (the hydrobromide salt of 5-MeO-DMT) or 5-MeO-DMT HCl (the hydrochloride salt of 5-MeO-DMT) and one or more pharmaceutically acceptable carriers or excipients.
  • the amorphous state does not revert to a crystalline form, and so the nature of the formulation is well understood.
  • the formulation is a spray dried formulation.
  • no more than 80% of the 5- MeO-DMT is released from the formulation by 4 minutes in water at 37°C.
  • no more than 80% of the 5-MeO-DMT is released from the formulation by 5, 6, 7, 8, 9 or 10 minutes in water at 37°C. In an embodiment, no more than 80% of the 5-MeO-DMT is released from the formulation by 5, 6, 7, 8, 9 or 10 minutes in a simulated nasal fluid. Beneficially, the 5-MeO-DMT is not released immediately, and indeed released relatively slowly. Beneficially, the person being treated receives the active substance over a duration of time. On some occasions, receiving the active substance, a psychoactive substance, over a very short period of time can be quite intense.
  • the particles of the formulation are larger than 10 microns in size.
  • the formulation does not substantially contain respirable fines (undesirable particles that could enter the lungs).
  • the 5-MeO-DMT HBr is non-hygroscopic.
  • the formulation comprises below about 5% (e.g., less that 5%, 4%, 3%, 2%, or 1%) moisture content by weight of the formulation.
  • the formulation is a free flowing formulation.
  • the formulation comprises at least about 10% ⁇ 5%, 15% ⁇ 5%, 20% ⁇ 10%, 30% ⁇ 10%, 40% ⁇ 10%, 50% ⁇ 10%, 60% ⁇ 10%, 70% ⁇ 10%, 80% ⁇ 10%, 90% ⁇ 10%, 95% or 99% by weight 5-MeO-DMT HBr.
  • the formulation comprises at least about 10% ⁇ 5%, 15% ⁇ 5%, 20% ⁇ 10%, 30% ⁇ 10%, 40% ⁇ 10%, 50% ⁇ 10%, 60% ⁇ 10%, 70% ⁇ 10%, 80% ⁇ 10%, 90% ⁇ 10%, 95% or 99%95% or 99% by weight 5-MeO-DMT HCl
  • the formulation upon administration to a nasal cavity of a subject the formulation exhibits a residence time.
  • the ratio of the low viscosity HPMC to high viscosity HPMC is in the ratio of 1:10 to 10:1 (e.g., 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1), optionally 1:4 to 4:1 (e.g., 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, or 4:1) and further optionally 1:2 to 2:1 (e.g., 0.5 ⁇ 0.25, 0.75 ⁇ 0.25, 1 ⁇ 0.25, 1.25 ⁇ 0.25, 1.5 ⁇ 0.25, 1.75 ⁇ 0.25, or 2 ⁇ 0.25).
  • 1:10 to 10:1 e.g., 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1
  • 1:4 to 4:1 e.g., 1:4,
  • the ratio of the low viscosity HPMC to high viscosity HPMC is in the ratio of 50:50, 45:55, 40:60, 35:65, 30:70 or 25:75.
  • the high viscosity HPMC has a viscosity greater or equal to about 20, 30, 40, 50 or 60 mPa•s, optionally where the HPMC is a HPMC containing about 7.0-12.0% (e.g., 7% ⁇ 1%, 8% ⁇ 1%, 9% ⁇ 1%, 10% ⁇ 1%, 11% ⁇ 1%, or 12% ⁇ 1%) hydroxypropyl content, about 28.0-30.0% (e.g., 28% ⁇ 2%, 29% ⁇ 2%, or 30% ⁇ 2%) methoxy content, and a viscosity of about 50 mPa•s.
  • 5-MeO-DMT salts have been found to be very soluble in water (e.g. some crystalline forms of the halide salts of 5-MeO-DMT have a solubility of > 400 mg/ml in water) and have very rapid dissolution profiles. While these properties can be desirable in solid oral or intravenous dosage formulations, they are not necessarily beneficial for intranasal formulations of 5-MeO-DMT. This is because 5-MeO-DMT can provide a very intense Mystical Experience in a subject.
  • the cellulose like/based excipients may have a viscosity to suit need, e.g. high, moderate or low viscosity or contain a mixture of these with different viscosities (e.g. a high and low viscosity).
  • the 5-MeO-DMT is preferentially soluble in the cellulose like/based excipients, and this delays/retards the API (i.e. 5-MeO-DMT) travelling across the nasal blood brain barrier.
  • the formulation should be free from respirable API fines (e.g.
  • the particles have a median diameter of greater than 500 ⁇ m, 250 ⁇ m, 100 ⁇ m, 50 ⁇ m, 40 ⁇ m, 30 ⁇ m, 25 ⁇ m, 20 ⁇ m, 15 ⁇ m, 10 ⁇ m, 5 ⁇ m, 1 ⁇ m or 0.5 ⁇ m.
  • the formulation comprises crystalline API dry blended with SDD comprising API/HPMC. Beneficially, this may provide for higher drug loadings within a single device.
  • the formulation is free from the one or more pharmaceutically acceptable carriers or excipients. 5-MeO-DMT is very likely to be treated as a controlled drug by Health authorities. The authorities would require the setting up of specific methodology for the prescribing and use of this drug in patients. When taken as prescribed by a licensed physician, controlled substances can effectively treat many conditions. However, over the past decade, in many countries, it can be seen that a drastic increase in controlled substance diversion, misuse, and abuse has occurred.
  • Abuse-deterrent formulations prevent inexperienced substance users from successfully ingesting substances via altered routes of administration, and thereby prevent associated overdoses and escalation of substance use, resulting in significant personal and public health benefits.
  • Abuse-deterrent formulations limit one or more forms of such abuse by reducing the attractiveness or drug-liking qualities of a controlled substance by: (1) Hindering the extraction of active ingredients; (2) Decreasing their bioavailability through product manipulation, thereby reducing the feeling of euphoria; (3) Preventing administration through alternative routes; (4) Making abuse of the manipulated product less attractive or rewarding.
  • Particular 5-MeO-DMT compositions as described herein in the form of, for example, spray dried dispersions of 5- MeO-DMT in combination with one or more pharmaceutically acceptable excipients benefit not only from the herein described advantageous properties of said dispersions, but also from the fact that said dispersions provide a deterrent to abuse.
  • the intimately mixed nature of the dispersions provides a barrier to the easy extraction of the active pharmaceutical ingredient.
  • a 5-MeO-DMT composition or formulation as described herein wherein said composition or formulation comprises a polyol and wherein said composition or formulation shows a strong reduction of mucosal irritation upon the intranasal, buccal, sublabial or sublingual administration thereof, compared with a composition or formulation without a polyol.
  • a method of reducing mucosal irritation in a subject upon intranasal, buccal, sublabial or sublingual administration of 5-MeO-DMT to the subject wherein said method comprises providing the 5-MeO-DMT in a composition or formulation as described herein, wherein said composition or formulation comprises a polyol.
  • a crystalline form of 5-MeO-DMT fumarate characterised by one or more peaks in an XRPD diffractogram at 13.0, 16.3 and 22.1°2 ⁇ 0.1°2 ⁇ as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 ⁇ .
  • a crystalline form of 5-MeO-DMT oxalate characterised by one or more peaks in an XRPD diffractogram at 13.0, 19.9 and 26.0°2 ⁇ 0.1°2 ⁇ as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 ⁇ .
  • a crystalline form of 5-MeO-DMT tosylate characterised by one or more peaks in an XRPD diffractogram at 19.3, 23.6 and 24.1 °2 ⁇ 0.1°2 ⁇ as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 ⁇ .
  • a crystalline form of 5-MeO-DMT glycolate characterised by one or more peaks in an XRPD diffractogram at 20.2, 21.1 and 23.4°2 ⁇ 0.1°2 ⁇ as measured by x- ray powder diffraction using an x-ray wavelength of 1.5406 ⁇ .
  • a crystalline form of 5-MeO-DMT saccharinate characterised by one or more peaks in an XRPD diffractogram at 8.7, 15.2 and 20.9°2 ⁇ 0.1°2 ⁇ as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 ⁇ .
  • a crystalline form of 5-MeO-DMT hydrochloride characterised by one or more peaks in an XRPD diffractogram at 9.2° ⁇ 0.1°, 12.2° ⁇ 0.1°, 14.1° ⁇ 0.1°, 15.0° ⁇ 0.1°, 18.5° ⁇ 0.1°, and 19.5° ⁇ 0.1°2 ⁇ as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 ⁇ .
  • a crystalline form of 5-MeO-DMT benzoate characterised by one or more peaks in an XRPD diffractogram at 17.5, 17.7 and 21.0°2 ⁇ 0.1°2 ⁇ as measured using an x-ray wavelength of 1.5406 ⁇ .
  • a dry powder formulation comprising 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, and polyvinylpyrrolidone (PVP).
  • a method of production of a formulation of 5-MeO-DMT comprising the steps of: a. Atomisation of a liquid mixture comprising 5-MeO-DMT to produce droplets; b. Contact between a hot gas and the droplets to dry the droplets; c. Optionally, the separation of the dried product from the drying medium; and d. Conditioning of the dried product.
  • the conditioning step comprises exposing the dried product to between 15 to 45°C and between 65% to 85% relative humidity (RH); optionally between 20 and 35°C and between 70 to 80% RH; and further optionally 25°C and 75% RH.
  • the conditioning step takes place for between 1 day and several weeks. In an embodiment, the conditioning step takes place for between 1 day and 1 week. In an embodiment, the conditioning step takes place for between 1 day and 3 days. In an embodiment, the conditioning step takes place for less than 1 day.
  • RH relative humidity
  • the conditioning step takes place for between 1 day and 1 week. In an embodiment, the conditioning step takes place for between 1 day and 3 days. In an embodiment, the conditioning step takes place for less than 1 day.
  • XRPD X-ray powder diffractograms
  • DSC differential scanning calorimetry
  • HPMC Hydroxypropyl methylcellulose
  • hypromellose refers to soluble methylcellulose ethers and is approved as an inactive ingredient. Without being bound by theory, HPMC is believed to act as a viscosity enhancer, and delays/slows mucociliary clearance.
  • the viscosity of the HPMC may be measured at 20 o C in an aqueous solution of 2 % (w/w). In certain instances, the viscosity of the HPMC may be measured at 2 % (w/v) in an aqueous solution at 20 o C.
  • the solid dispersions of the invention can be tuned/controlled by selection of a suitable molecular weight of polymer.
  • the solid dispersion comprises a polymer(s) having a low viscosity grade, e.g., a low molecular weight, such as a weight average molecular weight of less than or equal to 100,000 g/mol, less than or equal to 90,000 g/mol, less than or equal to 80,000 g/mol, less than or equal to 70,000 g/mol, less than or equal to 60,000 g/mol, less than or equal to 50,000 g/mol, less than or equal to 40,000 g/mol, less than or equal to 30,000 g/mol, less than or equal to 20,000 g/mol, less than or equal to 15,000 g/mol.
  • a low viscosity grade e.g., a low molecular weight, such as a weight average molecular weight of less than or equal to 100,000 g/mol, less than or equal to 90,000 g/mol, less than or equal to 80,000 g/mol, less than or equal to 70,000 g/mol, less than or
  • the lower limit of weight average molecular weight for low viscosity grade polymers may be from 1 ,000 g/mol, from 2,000 g/mol, from 4,000 g/mol, from 6,000 g/mol, from 8,000 g/mol, from 10,000 g/mol, from 12,000 g/mol, from 14,000 g/mol.
  • the low molecular weight polymer is a low molecular weight HPMC polymer, having a molecular weight within the above recite range, alone or as a polymer blend.
  • Examples of a low molecular weight HPMC polymers which can be used herein include, but are not limited to, AFFINISOLTM HPMC HME 15LV (water soluble; amorphous HPMC polymer with a molecular weight of less than 100 kDa; bulk density of 0.42 g/cc; D(0.5) of 104.49 pm), METHOCELTM E3 LV (2910 substitution type: 28-30% methoxy substitution, 7-12% hydroxypropyl substitution; viscosity of 4.0-6.0 mPa-s as 2% solution in water at 20 °C), METHOCELTM E6 premium LV (70,000-80,000 g/mol, 2910 substitution type: 28-30% methoxy substitution, 7-12% hydroxypropyl substitution; viscosity of 4.8- 7.2 mPa- s as 2% solution in water at 20°C), each available from DuPont, and PHARMACOAT® 606 (2910 substitution type: 28- 30% methoxy substitution, 7-12%
  • the selection of a low molecular weight polymer may provide solid dispersions adapted for immediate release or fast release of the 5-MeO-DMT.
  • immediate release may refer to dosage forms which release greater than 80 wt.% of the active ingredient within about 1 minute following administration
  • fast release may refer to dosage forms in which the release of 80 wt.% of the active ingredient takes place in a range of about 1 minute to about 5 minutes following administration.
  • solid dispersions comprising a low molecular weight polymer or polymer blend may be advantageously suited for freeze drying or spray drying preparation methods.
  • the solid dispersion comprises a polymer having a high viscosity grade, e.g., a high molecular weight, such as a weight average molecular weight of at least 150,000 g/mol, at least 200,000 g/mol, at least 250,000 g/mol, at least 300,000 g/mol, at least 350,000 g/mol, at least 400,000 g/mol, at least 450,000 g/mol, at least 500,000 g/mol, at least 550,000 g/mol, at least 600,000 g/mol, at least 650,000 g/mol, at least 700,000 g/mol, at least 750,000 g/mol, at least 800,000 g/mol, at least 850,000 g/mol, at least 900,000 g/mol, at least 950,000 g/mol, at least 1,000,000 g
  • a high molecular weight such as a weight average molecular weight of at least 150,000 g/mol, at least 200,000 g/mol, at least 250,000 g
  • the upper limit of molecular weight for high viscosity grade polymers is not particularly limited, but is typically up to 5,000,000 g/mol, 4,000,000 g/mol, 3,000,000 g/mol, or 2,000,000 g/mol.
  • the high molecular weight polymer is a high molecular weight HPMC polymer, having a molecular weight within the above recited range.
  • High molecular weight polymers or polymer blends may provide solid dispersions can be adapted for either fast release or extended-release dosage forms where it is desirable to release the 5-MeO-DMT over extended periods of time, such as for example over 10 minutes, 7 minutes, 10 minutes, 20 minutes, 30 minutes, or any range in between, or longer.
  • extended-release may refer to dosage forms in which the release of 80 wt.% of the active ingredient takes place in a range of about 5 minutes or longer, 10 minutes or longer, 15 minutes or longer, etc. following administration.
  • solid dispersions comprising a high molecular weight polymer or polymer blend may be advantageously suited for hot melt extrusion, spray drying, or freeze drying preparation methods.
  • Dry blending (giving a solid dispersion matrix) of cellulose based excipients, such as HPMC 2910, with the API at high concentrations up to approximately 95% wt:wt (excipient to 5-MeO-DMT) in the blend, beneficially slowed the dissolution release rate of the API relative to an unblended formulation. Care is needed when making dry blends to ensure blend uniformity and monitoring of any aggregation/agglomeration may be needed. Also, the nature of the blend needs to be assessed to ensure the physical properties work well with the delivery device and with scale up, e.g. if the resultant blend is prone to static charge build up, then the blend can be difficult to load into the delivery device without losses.
  • Intimate mix formulation e.g. spray drying, lyophilisation and/or hot melt extrusion with one or more suitable pharmaceutical excipients or carriers
  • intimate mix formulation e.g. spray drying, lyophilisation and/or hot melt extrusion with one or more suitable pharmaceutical excipients or carriers
  • These techniques are best known for generating amorphous solid dispersions with improved bioavailability and increased solubility. In the present case, with the intense Mystical Experiences associated with the API, this would not on the face of it appear beneficial.
  • dispersions comprise API loading of around 20% wt:wt (e.g.5-MeO-DMT to excipients) or below.
  • Lyophilisation formulations Amorphous 5-MeO-DMT salt formulations have been produced via lyophilisation processes.
  • Hot melt extrusion may be utilised to produce 5-MeO-DMT formulations according to the current invention and/or any embodiments thereof. Hot melt extrusion is the processing of polymeric materials above their glass transition temperature (Tg) in order to effect molecular level mixing of thermoplastic binders and/or polymers and active compounds.
  • Tg glass transition temperature
  • Spray dried dispersions Spray drying typically involves injecting a liquid composition of material into a chamber for contact with a drying fluid which is concurrently flowed through the chamber.
  • the injected wet material in the form of droplets contacts the stream of drying fluid so that the liquid passes from the droplets to the drying fluid stream, producing a spray dried product that is discharged from the drying chamber, and drying fluid effluent that likewise is discharged from the drying chamber.
  • spray dried dispersions of 5-MeO-DMT gave products with lower/reduced dissolution rates. This was unexpected because spray dried dispersions are generally developed to improve the solubility of low solubility products.
  • the formulation comprises two (or more) different HPMCs where these have different viscosities. In an embodiment, the formulation comprises two (or more) different HPMCs. In an embodiment, the formulation comprises two (or more) different HPMCs where these have different viscosities, and wherein the net viscosity of the mixture is spray dryable. In an embodiment, the formulation comprises two (or more) different HPMCs where these have different viscosities, wherein the net viscosity of the mixture is spray dryable, and wherein at least one of the HPMCs alone would not be readily suitable for spray drying.
  • the crystalline 5-MeO-DMT benzoate is characterised by one or more peaks in an X-ray powder diffraction (XRPD) diffractogram at a 2 ⁇ value of 17.5° ⁇ 0.1°, 17.7° ⁇ 0.1° and 21.0° ⁇ 0.1° using an X-ray wavelength of 1.5406 ⁇ .
  • XRPD X-ray powder diffraction
  • the 5-MeO-DMT salt is 5-MeO-DMT hydrobromide, and wherein the formulation comprises substantially the same dosage amount of the active 5-MeO-DMT cation.
  • the hydrobromide salt is substantially non-hygroscopic. It should be appreciated that different salts of 5-MeO-DMT will have different formula weights.
  • the hydrochloride, hydrobromide and benzoate have respectively formula weights of about 254.8 g/mol, 299.2 g/mol, 340.4 g/mol and the free base of 5-MeO-DMT 218.3 g/mol. So, this is the amount of substance that is required to give 1 mol of the active agent. So, for example for the salt, the dosage amount may be the equivalent amount of the free base delivered when the salt is taken. So 100mg dosage amount of 5-MeO-DMT corresponds to 117mg of the hydrochloride salt (i.e. both providing the same molar amount of the active substance). The greater mass of the salt needed is due to the larger formula weight of the hydrogen chloride salt (i.e.
  • the mass (mg) of 5-MeO-DMT refers to the mass of benzoate salt (and so the equivalent molar amount of the 5-MeO-DMT active agent). Accordingly, with reference to the other salts mentioned herein, the appropriate mass of the other salt can be scaled accordingly using ratios of the formula weights. These masses of salts are normally rounded up or down to suit need.
  • This rounding may be to the nearest whole, half, quarter or tenth of a milligram (mg).
  • splitting of a combined dose will typically be done to whole numbers so 3.5 and 6.5 mg (combined total of 10mg) may be formulated to 3 and 7 mg respectively.
  • the composition comprises the hydrochloride, phosphate, fumarate, oxalate, tartrate, benzenesulfonate, tosylate, glycolate, ketoglutarate, malate, saccharinate or succinate salt of 5-MeO-DMT.
  • the composition does not comprises a crystalline form of the hydrochloride, phosphate, fumarate, oxalate, tartrate, benzenesulfonate, tosylate, glycolate, ketoglutarate, malate, saccharinate or succinate salt of 5- MeO-DMT.
  • the 5-MeO-DMT is administered as the free base.
  • the 5-MeO-DMT is administered as a salt.
  • the 5-MeO-DMT is not administered as a crystalline salt. In an embodiment, the 5-MeO-DMT is not administered as a polymorphic salt form. In an embodiment, the 5-MeO-DMT is not administered as a polymorph of a 5-MeO-DMT salt. In an embodiment, the 5-MeO-DMT is administered as the benzoate, fumarate, citrate, acetate, succinate, halide, fluoride, chloride, bromide, iodide, oxalate, or triflate salt. In an embodiment, the 5-MeO-DMT is administered as the benzoate salt. In an embodiment, the 5-MeO-DMT is administered as the hydrochloride salt.
  • the 5-MeO-DMT is administered as the hydrobromide salt. In an embodiment, the 5-MeO-DMT salt is administered in an amorphous form. In an embodiment, the 5-MeO- DMT salt is not administered in a crystalline form. In an embodiment, the 5-MeO-DMT is not administered as a crystalline form of the benzoate salt. Crystalline forms of the benzoate salt are disclosed in WO2021250434 and are incorporated herein by reference. Crystalline forms of the hydrochloride salt are also disclosed in WO2021250434 and are incorporated herein by reference.
  • crystalline 5-MeO-DMT hydrochloride is characterised by peaks in an X-ray powder diffraction (XRPD) diffractogram at 2 ⁇ values of 9.2° ⁇ 0.1°, 12.2° ⁇ 0.1°, 14.1° ⁇ 0.1°, 15.0° ⁇ 0.1°, 18.5° ⁇ 0.1°, and 19.5° ⁇ 0.1°, as measured using an X-ray wavelength of 1.5406 ⁇ .
  • the salt anion is an aryl carboxylate.
  • the aryl carboxylate is substituted with one to three R groups.
  • the one or more R groups are independently selected from: alkynyl, carbonyl, aldehyde, haloformyl, alkyl, halide, hydroxy, alkoxy, carbonate ester, carboxylate, carboxyl, carboalkoxy, methoxy, hydroperoxy, peroxy, ether, hemiacetal, hemiketal, acetal, ketal, orthoester, methylenedioxy, orthocarbonate ester, carboxylic anhydride, carboxamide, secondary, tertiary or quaternary amine, primary or secondary ketimine, primary or secondary aldimine, imide, azide, azo, cyanate, isocyanate, nitrate, nitrile, isonitrile, nitrosooxy, nitro, nitroso, oxime, pyridyl, carbamate, sulfhydryl, sulfide, disulfide, sulfinyl, sulf
  • the one or more R groups are independently selected from: C 1 - C 6 alkyl, C 1 - C 6 alkoxy, C 1 - C 6 alkenyl or C1 - C6 alkynyl, and where each of these may be optionally substituted with one to three R groups as previously described.
  • the 5-MeO-DMT or the pharmaceutical composition comprising 5-MeO-DMT and one or more pharmaceutically acceptable carriers or excipients is for use in a method of one or more of: treating mental disorders, in particular treatment resistant depression, major depressive disorder, persistent depressive disorder, alcohol use disorder, anxiety disorder, post-traumatic stress disorder (PTSD), body dysmorphic disorder, obsessive- compulsive disorder, eating disorder and psychoactive substance abuse.
  • the disease or condition is: conditions caused by dysfunctions of the central nervous system, conditions caused by dysfunctions of the peripheral nervous system, conditions benefiting from sleep regulation (such as insomnia), conditions benefiting from analgesics (such as chronic pain), migraines, trigeminal autonomic cephalgias (such as short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), and short-lasting neuralgiform headaches with cranial autonomic symptoms (SUNA)), conditions benefiting from neurogenesis (such as stroke, traumatic brain injury, Parkinson’s dementia), conditions benefiting from anti- inflammatory treatment, depression, treatment resistant depression, anxiety, substance use disorder, addictive disorder, gambling disorder, eating disorders, obsessive-compulsive disorders, or body dysmorphic disorders, optionally the condition is SUNCT and/or SUNA, alcohol-related diseases and disorders, eating disorders, impulse control disorders, nicotine-related disorders, tobacco-related disorders, methamphetamine-related disorders, amphetamine-related disorders, cannabis-related
  • a composition or formulation as described herein in a method of treatment wherein the method of treatment comprises interaction of a patient with one or more components of a prescription digital therapeutic (PDT).
  • a prescription digital therapeutic (PDT) for use in a method of medical treatment, wherein the method comprises: administering a dose of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, to a patient in need thereof; monitoring the interaction of the patient with one or more components of the PDT via one or more electronic devices or inputs linked thereto; assessing the interaction of the patient with the one or more components of the PDT; determining the response of the patient to the administered dose of the 5- MeO-DMT based on the assessment of the interaction of the patient with the one or more components of the PDT; and recommending a dose of the 5-MeO-DMT for further administration, or a cessation of further doses of the 5- MeO-DMT.
  • 5-MeO-DMT is administered together with the PDT.
  • the method comprises the detection of relapse.
  • the method comprises recommending a dose of the 5-MeO- DMT to enhance the patient response to the treatment.
  • the one or more components of the PDT comprise: guided meditation; breathing exercises; neuro/bio-feedback exercises; journaling; surveys/questionnaires; video and/or audio content; remote contact with one or more healthcare professionals (HCPs) and/or one or more peers who have experienced 5-MeO-DMT benzoate treatment (hereafter 'peers'); therapy tasks, such as the Values Card Sort Task; remote cognitive behavioural therapy (CBT); Al chat tools; and automated reminders and/or alerts.
  • HCPs healthcare professionals
  • CBT remote cognitive behavioural therapy
  • a prescription digital therapeutic is a prescription-only software that delivers evidence-based therapeutic intervention(s) to prevent, manage or treat a medical disorder or disease.
  • PDT is a prescription-only software that delivers evidence-based therapeutic intervention(s) to prevent, manage or treat a medical disorder or disease.
  • 5-MeO-DMT i.e. a potent psychoactive/psychedelic substance
  • patient preparation prior to treatment with 5-MeO-DMT is believed to be important for optimal experience and outcomes. That is, the 5-MeO-DMT experience is visually and experientially all encomPa•ssing, with limited connection to the physical environment.
  • the intensity of the experience with 5-MeO-DMT is such that conscious control or direction of the experience is not possible, therefore there is perhaps a greater need for pre-therapy preparation to enter the experience in the right sub-conscious state/mindset.
  • Administration of 5-MeO-DMT is believed to generate a neuroplastic effect such that delivery of psychotherapy in the weeks after treatment generates a greater impact on outcomes. Long term, identifying the return of symptoms and the need for retreatment or therapy may be important for delivering sustained recovery.
  • the methods are designed to be delivered prior to and after administration of 5-MeO-DMT, for psychological/psychiatric conditions via a digital platform and uses actively and passively entered data to support preparation, post-treatment integration, and ongoing therapy to enhance and sustain patient response to treatment.
  • the methods are also useful in screening potential candidates prior to treatment with 5-MeO-DMT for likelihood and/or type of treatment response.
  • a combination of active and passive data is used to generate a response profile that indicates whether treatment with 5-MeO-DMT will be safe and effective.
  • the method may provide a clinician with a recommendation on the optimal treatment protocol (therapy, drug, dose etc), and determines any settings for automated preparation, in-experience setting and post-treatment integration.
  • the methods support integration through automated content, therapy, and connecting individuals to therapists remotely, and to others who have also experienced 5-MeO-DMT therapy.
  • the method additionally comprises the interaction of the patient with one or more components of the PDT occurs prior to administration of the dose of the 5-MeO-DMT.
  • the method additionally comprises the interaction of the patient with one or more components of the PDT occurs prior to administration of the dose of the 5-MeO-DMT, wherein administration of the dose of the 5-MeO-DMT only occurs if the interaction of the patient with one or more components of the PDT indicates the patient is likely to respond favourably to such administration.
  • Favourable (or disfavourable) response may for example be determined in an appropriate manner, e.g. as suggested by one or more of: Favourable response may for example determined in an appropriate manner, e.g. as suggested by one or more of: lower scores on symptom severity at the start of treatment could indicate good response, i.e.
  • an interaction with Al chat tool wherein the patient responds negatively to a series of questions indicates that they are unlikely to respond favourably to 5-MeO-DMT administration.
  • the treatment change is initiated by, or with the input from, one or more HCPs. In an embodiment, the treatment change is initiated by, or with the input from, one or more HCPs and one or more algorithms. In an embodiment, the treatment change comprises a change in one or more of: dose of the 5-MeO-DMT; frequency of administration of the 5-MeO-DMT; form of administration of the 5-MeO-DMT; and components of the PDT.
  • the change in the one or more components of the PDT is selected from a change in one or more of: guided meditation; breathing exercises; neuro/bio-feedback exercises; journaling; surveys/questionnaires; video and/or audio content; remote contact with one or more HCPs and/or one or more peers who have experienced 5- MeO-DMT treatment (hereafter 'peers'); therapy tasks, such as the Values Card Sort Task; remote cognitive behavioural therapy (CBT); Al chat tools; and automated reminders and/or alerts.
  • the one or more electronic devices are selected from: smart device; smartphone; smartwatch; smart glasses; smart ring; smart patch; home hub smart device (e.g. Amazon AlexaTM); fitness tracker; personal computer; tablet (e.g.
  • An active nasal delivery device comprising the spray dried dry powder pharmaceutical formulation of any one of items 1 to 21.
  • the active nasal delivery device of item 27 for use in a method of treating a disease or condition selected from: conditions caused by dysfunctions of the central nervous system, conditions caused by dysfunctions of the peripheral nervous system, conditions benefiting from sleep regulation (such as insomnia), conditions benefiting from analgesics (such as chronic pain), migraines, trigeminal autonomic cephalgias (such as short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), and short-lasting neuralgiform headaches with cranial autonomic symptoms (SUNA)), conditions benefiting from neurogenesis (such as stroke, traumatic brain injury, Parkinson’s dementia), conditions benefiting from anti-inflammatory treatment, depression, treatment resistant depression, anxiety, substance use disorder, addictive disorder, gambling disorder, eating disorders, obsessive-compulsive disorders, or body dysmorphic disorders, optionally the condition is SUNCT and/or SUNA, alcohol-related diseases and disorders, eating disorders, impulse control disorders, nicotine-related disorders, tobacco- related disorders, methamphetamine-
  • the active nasal delivery device of item 28 for use in a method of treating a disease or condition selected from: conditions caused by dysfunctions of the central nervous system, conditions caused by dysfunctions of the peripheral nervous system, conditions benefiting from sleep regulation (such as insomnia), conditions benefiting from analgesics (such as chronic pain), migraines, trigeminal autonomic cephalgias (such as short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), and short-lasting neuralgiform headaches with cranial autonomic symptoms (SUNA)), conditions benefiting from neurogenesis (such as stroke, traumatic brain injury, Parkinson’s dementia), conditions benefiting from anti-inflammatory treatment, depression, treatment resistant depression, anxiety, substance use disorder, addictive disorder, gambling disorder, eating disorders, obsessive-compulsive disorders, or body dysmorphic disorders, optionally the condition is SUNCT and/or SUNA, alcohol-related diseases and disorders, eating disorders, impulse control disorders, nicotine-related disorders, tobacco- related disorders, methamphetamine-
  • a dry blended dry powder pharmaceutical formulation comprising 5-MeO-DMT, or pharmaceutically acceptable salt thereof, and silicon dioxide, wherein the formulation may comprise one or more pharmaceutically acceptable carriers or excipients.
  • the dry blended dry powder pharmaceutical formulation of any one of items 31 to 34 wherein the formulation comprises a low viscosity methyl cellulose, and a high viscosity methyl cellulose.
  • the dry blended dry powder pharmaceutical formulation of any one of items 31 to 35 wherein the formulation comprises a cellulose like/based excipient; optionally HPMC, further optionally a high viscosity HPMC.
  • the dry blended dry powder pharmaceutical formulation of item 36 wherein the formulation comprises a low viscosity HPMC and a high viscosity HPMC.
  • the dry blended dry powder pharmaceutical formulation of item 37 wherein the ratio of the low viscosity HPMC to high viscosity HPMC is in the ratio of 1:10 to 10:1, optionally 1:4 to 4:1 and further optionally 1:2 to 2:1.
  • the dry blended dry powder pharmaceutical formulation of item 38 wherein the ratio of the low viscosity HPMC to high viscosity HPMC is in the ratio of 50:50, 45:55, 40:60, 35:65, 30:70 or 25:75.
  • the dry blended dry powder pharmaceutical formulation of item 39 wherein the high viscosity HPMC has a viscosity greater or equal to about 20, 30, 40, 50 or 60 mPa•s, optionally where the HPMC is a HPMC containing about 7.0-12.0% hydroxypropyl content, about 28.0-30.0% methoxy content, and a viscosity of about 50 mPa•s.
  • the dry blended dry powder pharmaceutical formulation of item 40 wherein the low viscosity HPMC has a viscosity less than about 20, 15, 10, 5, 1 mPa•s, optionally where the HPMC is a HPMC containing about 7.0-12.0% hydroxypropyl content, about 28.0-30.0% methoxy content, and a viscosity of about 4.8-7.2 mPa•s.
  • the dry blended dry powder pharmaceutical formulation of item 42 wherein the formulation comprises about 1-10%, 2-5% or 3% polyol by weight, optionally about 3% sorbitol or mannitol or isomalt by weight.
  • An active nasal delivery device comprising the dry blended dry powder pharmaceutical formulation of any one of items 31 to 51.
  • the active nasal delivery device of item 52 or item 53 wherein the formulation comprises below about 5% moisture content by weight of the formulation.
  • the active nasal delivery device of item 55 wherein the active nasal delivery device comprises a crystalline 5-MeO-DMT salt selected from: - a crystalline form of 5-MeO-DMT benzoate, characterised by one or more peaks in an XRPD diffractogram at 17.5, 17.7 and 21.0°2 ⁇ 0.1°2 ⁇ as measured using an x-ray wavelength of 1.5406 ⁇ ; - a crystalline form of 5-MeO-DMT hydrochloride, characterised by one or more peaks in an XRPD diffractogram at 9.2° ⁇ 0.1°, 12.2° ⁇ 0.1°, 14.1° ⁇ 0.1°, 15.0° ⁇ 0.1°, 18.5° ⁇ 0.1°, and 19.5° ⁇ 0.1°2 ⁇ as measured by x-ray powder diffraction using an x-ray wavelength of 1.5406 ⁇ ; or - a crystalline form of 5-MeO-DMT hydrobromide, characterised by one or more peaks in an XRPD diffractogram at 14.6, 16.8, 20.
  • the active nasal delivery device of any one of items 52 to 56 wherein the active nasal delivery device comprises: a dispenser outlet; an air expeller for generating a flow of air while the device is being actuated; and at least one reservoir that contains a single dose of formulation.
  • the active nasal delivery device of any one of items 52 to 57 wherein the active nasal delivery device comprises: a dispenser outlet; an air expeller for generating a flow of air while the device is being actuated, said air expeller including a piston that slides in an air chamber between a rest position and a dispensing position, said air chamber including a cylindrical body in which said piston slides in airtight manner; and at least one reservoir that contains a single dose of formulation, said reservoir including an air inlet that is connected to said air expeller, and a formulation outlet that is connected to said dispenser outlet, said air inlet including a formulation retainer member for retaining the formulation in the reservoir until the formulation is dispensed, and said formulation outlet being closed by a closure element that is force fitted in the formulation outlet of the reservoir; said
  • the active nasal delivery device of item 58 for use in a method of treating a disease or condition selected from: conditions caused by dysfunctions of the central nervous system, conditions caused by dysfunctions of the peripheral nervous system, conditions benefiting from sleep regulation (such as insomnia), conditions benefiting from analgesics (such as chronic pain), migraines, trigeminal autonomic cephalgias (such as short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), and short-lasting neuralgiform headaches with cranial autonomic symptoms (SUNA)), conditions benefiting from neurogenesis (such as stroke, traumatic brain injury, Parkinson’s dementia), conditions benefiting from anti-inflammatory treatment, depression, treatment resistant depression, anxiety, substance use disorder, addictive disorder, gambling disorder, eating disorders, obsessive-compulsive disorders, or body dysmorphic disorders, optionally the condition is SUNCT and/or SUNA, alcohol-related diseases and disorders, eating disorders, impulse control disorders, nicotine-related disorders, tobacco- related disorders, methamphetamine
  • the active nasal delivery device of item 58 for use in a method of treating a disease or condition selected from: conditions caused by dysfunctions of the central nervous system, conditions caused by dysfunctions of the peripheral nervous system, conditions benefiting from sleep regulation (such as insomnia), conditions benefiting from analgesics (such as chronic pain), migraines, trigeminal autonomic cephalgias (such as short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), and short-lasting neuralgiform headaches with cranial autonomic symptoms (SUNA)), conditions benefiting from neurogenesis (such as stroke, traumatic brain injury, Parkinson’s dementia), conditions benefiting from anti-inflammatory treatment, depression, treatment resistant depression, anxiety, substance use disorder, addictive disorder, gambling disorder, eating disorders, obsessive-compulsive disorders, or body dysmorphic disorders, optionally the condition is SUNCT and/or SUNA, alcohol-related diseases and disorders, eating disorders, impulse control disorders, nicotine-related disorders, tobacco- related disorders, methamphetamine
  • XRPD X-ray powder diffraction
  • a pharmaceutical formulation comprising 5-MeO-DMT HCl Form IV, wherein the formulation is characterised by one or more peaks in an X-ray powder diffraction (XRPD) diffractogram at 2 ⁇ values of 8.7° ⁇ 0.1°, 10.1° ⁇ 0.1°, 11.1° ⁇ 0.1°, 13.4° ⁇ 0.1° or 16.9° ⁇ 0.1° using an X-ray wavelength of 1.5406 A.
  • XRPD X-ray powder diffraction
  • the term “active nasal delivery device” refers to a nasal delivery device configured to actively deliver a formulation following actuation by a subject/patient or third party. This contrasts with a passive nasal delivery device wherein delivery of a formulation relies on inhalation by the subject/patient to draw the formulation out of the device.
  • these terms refer to an amount of the composition sufficient to achieve a treatment response as compared to the response obtained without administration of the composition.
  • the quantity of a given composition described herein that will correspond to such an amount may vary depending upon various factors, such as the given agent, the pharmaceutical formulation, the route of administration, the type of disease or disorder, the identity of the subject (e.g., age, sex, weight) or host being treated, and the like.
  • An “amount sufficient to,” or the like, of a composition of the present disclosure also include an amount that results in a beneficial or desired result in a subject as compared to a control (e.g., a decrease in the score on the Montgomery-Asberg Depression Rating Scale).
  • Figure 8 shows a DSC thermogram for the SDD of Example 2.
  • Figure 9 shows an XRPD for the SDD of Example 3.
  • Figure 10 shows a DSC thermogram for the SDD of Example 3.
  • Figure 11 shows an XRPD for the SDD of Example 4.
  • Figure 12 shows a DSC thermogram for the SDD of Example 4.
  • Figure 13 shows an XRPD for the SDD of Example 5.
  • Figure 14 shows an XRPD for the SDD of Example 6.
  • Figure 15 shows the dissolution profile of the SDD of Example 6.
  • Figure 16 shows an XRPD for the SDD of Example 7.
  • Figure 17 shows an XRPD for the SDD of Example 8.
  • Figure 18 shows an XRPD for the SDD of Example 9.
  • Figure 19 shows an XRPD for the SDD of Example 10.
  • Figure 32 shows a DSC thermogram for the SDD of Example 14.
  • Figure 33 shows the dissolution profile for the SDD of Example 14.
  • Figure 34 shows an XRPD of the SDD of Example 15.
  • Figure 35 shows a DSC thermogram for the SDD of Example 15.
  • Figure 36 shows the dissolution profile for the SDD of Example 15.
  • Figure 37 shows an XRPD of the lyophilized dispersion of Example 18.
  • Figure 38 shows a DSC thermogram for the lyophilized dispersion of Example 18.
  • Figure 39 shows an XRPD of the lyophilized dispersion of Example 19.
  • Figure 40 shows a DSC thermogram for the lyophilized dispersion of Example 19.
  • Figure 41 shows an XRPD of the lyophilized dispersion of Example 20.
  • Figure 57 shows the dissolution profile of a 5-MeO-DMT formulation comprising sorbitol and methyl cellulose.
  • Figure 58 shows an XRPD diffractogram overlay of the three previously known crystalline forms of 5-MeO-DMT HCl (Forms I-III) and the XRPD diffractogram pattern exhibited by the 5-MeO-DMT HCl formulation of Example 27 following storage at 25°C/60%RH for 6 months.
  • Example 2 Spray drying of 5-MeO-DMT oxalate salt with HPMC Spray drying 5-MeO-DMT oxalate and HPMC (Pharmacoat 606) in water produced a 50% wt:wt API to excipient SDD.
  • Example 3 Spray drying of 5-MeO-DMT hydrobromide salt with PVP Spray drying 5-MeO-DMT hydrobromide and polyvinylpyrrolidone (PVP) in water produced a 50% wt:wt API to excipient SDD.
  • PVP polyvinylpyrrolidone
  • Example 5 Spray drying of 5-MeO-DMT benzoate salt with HPMC mixtures Spray drying of 5-MeO-DMT benzoate with a mixture of HPMC 2910 in water produced a 50% wt:wt API to excipient SDD.
  • the spray drying parameters were as below: Feed Solution Sample Reference 30130-08-01 Pharmacoat 606 1.19g Metolose 60SH50 1.19g 5-MeO-DMT Benzoate 2.38g Water (deionized) 95.24g Spray Drying Parameters Instrument Procept Nozzle Ultrasonic Inlet Flow (m 3 /min) 0.7 Inlet Temperature (°C) 125 Cyclone Gas Pressure (bar) 0.5 Pump Speed (RPM) 60 (2g per minute) Nozzle Power % 98% Yield Yield (%) 34.7
  • the process for producing the feed solution was as follows: the required mass of water was weighed into a 50 mL vial.
  • Example 6 Spray drying of 5-MeO-DMT benzoate salt with HPMC mixtures Spray drying of 5-MeO-DMT benzoate with a mixture of HPMC 2910 in water produced a 50% wt:wt API to excipient SDD.
  • Example 7 Spray drying of 5-MeO-DMT benzoate salt with HPMCAS Spray drying of 5-MeO-DMT benzoate with hydroxypropyl methylcellulose acetate succinate (HPMCAS) M produced a 50% wt:wt API to excipient SDD. HPMCAS is produced in three substitution grades: L, M and H.
  • the spray drying parameters were as below: Feed Solution Sample Reference 30120-08-03 HPMCAS M 2.38g 5-MeO-DMT Benzoate 2.38g Water (deionized) 47.62g Acetone 47.62g Spray Drying Parameters Instrument Procept Nozzle Ultrasonic Inlet Flow (m 3 /min) 0.7 Inlet Temperature (°C) 125 Cyclone Gas Pressure (bar) 0.5 Pump Speed (RPM) 60 (2g per minute) Nozzle Power % 96% Yield Yield (%) 44.7
  • the process for producing the feed solution was as follows: the required mass of acetone was weighed into a 50 mL vial. The required mass of HPMC-AS was added to the acetone whilst stirring and allowed to fully dissolve.
  • Example 8 Spray drying of 5-MeO-DMT benzoate salt with HPMCAS/Metolose Spray drying of 5-MeO-DMT benzoate with HPMCAS M and Metolose 60SH50 in water produced a 50% wt:wt API to excipient SDD.
  • the spray drying parameters were as below: Feed Solution HPMCAS M 1.19g Metolose 60SH50 1.19g 5-MeO-DMT Benzoate 2.38g Water (deionized) 47.62g Acetone 47.62g Spray Drying Parameters Instrument Procept Nozzle Ultrasonic Inlet Flow (m 3 /min) 0.7 Inlet Temperature (°C) 125 Cyclone Gas Pressure (bar) 0.5 Nozzle Power % 96% Yield Yield (%) 29.2
  • the process for producing the feed solution was as follows: the required mass of acetone was weighed into a 50 mL vial. The required mass of HPMC-AS was added to the acetone whilst stirring and allowed to fully dissolve.
  • Example 9 Spray drying of 5-MeO-DMT benzoate salt with HPMCAS/Metolose Spray drying of 5-MeO-DMT benzoate with HPMCAS M and Metolose 60SH50 in water produced a 50% wt:wt API to excipient SDD.
  • the spray drying parameters were as below: Feed Solution HPMCAS M 1.785g Metolose 60SH50 1.595g 5-MeO-DMT benzoate 2.38g Water (deionized) 47.62gg Acetone 47.62g Spray Drying Parameters Instrument Procept Nozzle Ultrasonic Inlet Flow (m 3 /min) 0.7 Inlet Temperature (°C) 125 Cyclone Gas Pressure (bar) 0.5 Nozzle Power % 96% Yield Yield (%) 27.2
  • the process for producing the feed solution was as follows: the required mass of acetone was weighed into a 50 mL vial. The required mass of HPMC-AS was added to the acetone whilst stirring and allowed to fully dissolve.
  • Example 10 Spray drying of 5-MeO-DMT benzoate salt with HPMC mixtures Spray drying of 5-MeO-DMT benzoate with a mixture of HPMC 2910 in water produced a 10% wt:wt API to excipient SDD.
  • the spray drying parameters were as below: SDD Composition Sample Reference 3815-02-01 Pharmacoat 606 67.5% Metolose 60SH50 22.5% 5-MeO-DMT Benzoate 10% Spray Drying Parameters Instrument Procept Nozzle Ultrasonic Inlet Flow (m 3 /min) 0.7 Inlet Temperature (°C) 125 Cyclone Gas Pressure (bar) 0.5 Pump Speed (RPM) 60 (2g per minute) Nozzle Power % 98% Feed Sock % solids Yield Yield (%) 58%
  • the process for spray drying the feed solution was as follows: the required mass of water was weighed into a 50 mL vial. The required mass of HPMC and Metolose were added to the water whilst stirring and allowed to fully dissolve.
  • Example 11 Spray drying of 5-MeO-DMT benzoate salt with HPMC mixtures Spray drying of 5-MeO-DMT benzoate with a mixture of HPMC 2910 in water produced a 30% wt:wt API to excipient SDD.
  • the spray drying parameters were as below: SDD Composition Sample Reference 3815-02-02 Pharmacoat 606 52.5% Metolose 60SH50 17.5% 5-MeO-DMT Benzoate 30% Spray Drying Parameters Instrument Procept Nozzle Ultrasonic Inlet Flow (m 3 /min) 0.7 Inlet Temperature (°C) 125 Cyclone Gas Pressure (bar) 0.5 Pump Speed (RPM) 60 (2g per minute) Nozzle Power % 98% Feed Sock % solids Yield Yield (%) 60%
  • the process for spray drying the feed solution was as follows: the required mass of water was weighed into a 50 mL vial. The required mass of HPMC and metolose were added to the water whilst stirring and allowed to fully dissolve.
  • Example 12 Spray drying of 5-MeO-DMT benzoate salt with HPMC mixtures Spray drying of 5-MeO-DMT benzoate salt with a mixture of HPMC 2910 in water produced a 50% wt:wt API to excipient SDD.
  • the spray drying parameters were as below: SDD Composition Example Reference 3815-02-02 Pharmacoat 606 37.5% Metolose 60SH50 12.5% 5-MeO-DMT Benzoate 50% Spray Drying Parameters Instrument Procept Nozzle Ultrasonic Inlet Flow (m 3 /min) 0.7 Inlet Temperature (°C) 125 Cyclone Gas Pressure (bar) 0.5 Pump Speed (RPM) 60 (2g per minute) Nozzle Power % 98% Feed Sock % solids Yield Yield (%) 52%
  • the spray drying process was as follows: the required mass of water was weighed into a 50 mL vial. The required mass of HPMC and metolose were added to the water whilst stirring and allowed to fully dissolve.
  • the SDD produced was partially crystalline ( Figure 25) with a dissolution profile (Figure 26) that shows that ⁇ 80% release has occurred by ⁇ 4.5 minutes, compared with ⁇ 4 minutes for the SDD of Example 6, ⁇ 10 minutes for the SDD of Example 10 and ⁇ 6.5 minutes for the SDD of Example 11.
  • the DSC thermogram for the SDD ( Figure 27) shows a small peak at ⁇ 140° C indicating the presence of crystalline API. Such a peak is not seen in the equivalent HBr or HCl salt formulations.
  • Example 14 Spray drying of 5-MeO-DMT benzoate salt with HPMC mixtures Spray drying of 5-MeO-DMT benzoate salt with a mixture of HPMC 2910 and sorbitol in water produced a 30% wt:wt API to excipient SDD.
  • Figure 42 shows a DSC thermogram for the lyophilized dispersion of Example 20.
  • Example 21 Lyophilisation of Oxalate salt with trehalose Lyophilisation of Oxalate salt with lactose trehalose in water to produce a 50% wt:wt API lyophilized dispersion.
  • Figure 48 shows a DSC thermogram for the lyophilized dispersion of Example 23.
  • Example 24 Stable amorphous formulations of 5-MeO-DMT HBr and HCl
  • the formulations of 5-MeO-DMT HBr and HCl as described in Examples 16 and 17 were stored for 1 month at (i) 25°C/60%RH or (ii) 2-8°C.
  • the formulations comprised 50% by weight of either 5-MeO-DMT HBr or HCl, a 3:1 ratio of HPMC 606: Metolose 60SH 50 and 3% sorbitol.
  • the XRPD showed that the formulation remained amorphous.
  • Analysis by TGA, mDSC, HPLC and scanning electron microscope (SEM) imaging further confirmed that the formulation remained amorphous.
  • a state-stable amorphous formulation of 5-MeO-DMT suitable for storage at, at least, 25°C/60%RH for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months wherein the formulation comprises 5-MeO-DMT HBr or 5-MeO-DMT HCl.
  • a stable amorphous formulation of 5-MeO-DMT In an embodiment, there is provided a state-stable amorphous formulation of 5-MeO-DMT. In an embodiment, there is provided a stable amorphous formulation of 5-MeO-DMT suitable for storage at, at least, 25°C/60%RH for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 24 months. In an embodiment, there is provided an amorphous 5-MeO-DMT HBr formulation. In an embodiment, there is provided a method for producing a stable amorphous formulation of 5-MeO-DMT, as described herein.
  • Example 25 Method for the determination of dissolution rate
  • the dissolution rate of SDD was determined using a method comprising the use of a UV- fibre optic-based dissolution apparatus (one such suitable device is the Rainbow® Dynamic Dissolution Monitor by Pion Inc) and simulated nasal fluid.
  • the simulated nasal fluid comprises 7.45g/L NaCl, 1.29g/L KCl, 0.32g/L CaCl2 x 2H2O and deionised water.
  • the dissolution apparatus was set up with a 2mm probe to measure the dissolution rate.10mg of the SDD (5mg API) was transferred into 5mL of simulated nasal fluid, heated to a constant temperature of 37°C and stirred at 150 RPM using a crossed stirrer bar. Measurements were taken at 3s intervals for 130 intervals followed by 60 measurements taken at 10s intervals for a total time of 16 minutes and 30s. Detection of dissolution is by UV absorbance.
  • the SDD is a 5-MeO-DMT SDD.
  • said 5-MeO-DMT SDD may be as described previously or subsequently herein.
  • a 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5mm probe may be used.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20mg of the SDD may be used.
  • 1 to 100mg of the SDD may be used.
  • 1-100mL of simulated nasal fluid is used.
  • 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20mL of nasal fluid is used.
  • the constant temperature used is 37°C +/- 1, 2, 3, 4 or 5°C.
  • the solution is stirred at 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180190 or 200 RPM. In an embodiment, the solution is stirred at 50-200 RPM. In an embodiment, measurements are taken at 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10s intervals for 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180190 or 200 intervals followed by 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180190 or 200 measurements taken at 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10s intervals.
  • Example 26 Method for the determination of crystalline content of psychedelic formulations.
  • DSC Differential scanning calorimetry
  • Tg glass transition temperatures
  • the enthalpy obtained from the melt of crystalline 5-MeO-DMT in a formulation was reduced with increased heating rate indicating that a DSC heating rate of 10 °C per minute is not suitable.
  • heating rates of above 10 °C per minute is required in order to evaluate the crystalline content of psychedelic formulations.
  • the optimal heating rate has been discovered to be between 100 and 200°C per minute, between 110 and 190°C per minute, between 120 and 180°C per minute, between 130 and 170°C per minute or between 140 and 160°C per minute.
  • the optimal heating rate for the determination of crystalline content of a psychedelic formulation by DSC is 150°C per minute.
  • a method of determining the crystalline content of a 5-MeO-DMT formulation by DSC is 150°C per minute. In an embodiment, there is provided a method of determining the crystalline content of a spray dried 5-MeO-DMT formulation by DSC is 150°C per minute.
  • Example 27 Further stability testing of amorphous formulations of 5-MeO-DMT HBr and HCl The formulations of 5-MeO-DMT HBr and HCl as described in Examples 16 and 17 were stored for 2 months at (i) 25°C/60%RH or (ii) 2-8°C.
  • the formulations comprised 50% by weight of either 5-MeO-DMT HBr or HCl, a 3:1 ratio of HPMC 606: Metolose 60SH 50 and 3% sorbitol.
  • Example 27a Further stability testing of a formulation of 5-MeO-DMT HCl
  • the 5-MeO-DMT HCl formulations of Example 27 were investigated following storage at 6 months.
  • the formulation stored at 2-8°C remained amorphous whilst the formulation stored at 25°C/60%RH exhibited recrystallisation (28.8% crystallinity) into a new crystalline form of 5-MeO-DMT HCl.
  • Three crystalline forms of 5-MeO-DMT HCl have previously been characterised, see for example US11,518,743.
  • Figure 58 shows an XRPD diffractogram overlay of the three previously known crystalline forms of 5-MeO-DMT HCl (Forms I-III) and the XRPD diffractogram pattern exhibited by the 5-MeO-DMT HCl formulation of Example 27 following storage at 25°C/60%RH for 6 months.
  • the Tables below show the XRPD diffractogram patterns of Forms I-III and that of the new Form, and their respective relative intensities: HCl Form I HCl Form II HCl Form III Angle d Value Rel. Angle d Value Rel. Angle d Value Rel.
  • crystalline 5-MeO-DMT HCl characterised by one or more peaks in an X-ray powder diffraction (XRPD) diffractogram at 2 ⁇ values of 11.1° ⁇ 0.1°, 13.4° ⁇ 0.1° or 16.9° ⁇ 0.1° using an X-ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT HCl characterised by one or more peaks in an X-ray powder diffraction (XRPD) diffractogram at 2 ⁇ values of 8.7° ⁇ 0.1°, 11.1° ⁇ 0.1°, 13.4° ⁇ 0.1° or 16.9° ⁇ 0.1° using an X- ray wavelength of 1.5406 A.
  • crystalline 5-MeO-DMT HCl characterised by one or more peaks in an X-ray powder diffraction (XRPD) diffractogram at 2 ⁇ values of 8.7° ⁇ 0.1°, 10.1° ⁇ 0.1°, 11.1° ⁇ 0.1°, 13.4° ⁇ 0.1° or 16.9° ⁇ 0.1° using an X-ray wavelength of 1.5406 A.
  • XRPD X-ray powder diffraction
  • the peak values may be ⁇ 0.1°, ⁇ 0.2° or ⁇ 0.3°.
  • a pharmaceutical formulation comprising 5-MeO-DMT HCl Form IV, wherein the formulation is characterised by one or more of the peaks in the Table above characteristic of Form IV.
  • a dispenser device optionally for dispensing a formulation or composition as described herein, the dispenser device comprising: a formulation or composition as described herein; a dispenser outlet (10); an air expeller (20) for generating a flow of air while the device is being actuated, said air expeller (20) including a piston (21) that slides in an air chamber (22) between a rest position and a dispensing position, said air chamber (22) including a cylindrical body (222) in which said piston (21) slides in airtight manner; and at least one reservoir (30) that contains a single dose of composition, said reservoir (30) including an air inlet (31) that is connected to said air expeller (20), and a composition outlet (32) that is connected to said dispenser outlet (10), said air inlet (31) including a composition retainer member (40) for retaining the composition in the reservoir (30) until the composition is dispensed, and said composition outlet (32) being closed by a closure element (50) that is force fitted in the composition outlet (32) of the reservoir (30); said device further including
  • an active nasal delivery device as described herein comprising one or more markings, said markings being visible when the active nasal delivery device is in the resting state and not visible following successful actuation of said active nasal delivery device.
  • the absence from view of said markings represents successful actuation of the active nasal delivery device.
  • the one or more markings may be as described herein.
  • an intranasal delivery system optionally comprising an active nasal delivery device as described herein, comprising: a dry powder formulation comprising a plurality of powder particles of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof; and an active nasal delivery device, optionally as described herein, configured to deliver the particles to the turbinates and olfactory region of the nasal cavity of a subject at a single actuation; wherein the system is operably configured to emit a powder plume comprising 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, having one or more of: a plume geometry of: angle: 20 to 45 degrees; width: 25 to 55 mm; a spray pattern of: Distance 40mm: Distance 70mm: Dmin(mm): 15 to 25 Dmin(mm): 15 to 40 Dmax(mm): 20 to 55 Dmax(mm): 35 to 60 Area (mm 2 ): 390 to 900 Area (mm 2 ): 800-1600 Area%: 2 to 15 Area%
  • an intranasal delivery system optionally comprising an active nasal delivery device as described herein, comprising: a dry powder formulation comprising a plurality of powder particles of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof; and an active nasal delivery device, optionally as described herein, configured to deliver the particles to the turbinates and olfactory region of the nasal cavity of a subject at a single actuation; wherein the system is operably configured to emit a powder plume comprising 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, having one or more of: a plume geometry of: angle: 20 to 45 degrees; width: 25 to 55 mm; a spray pattern of: Distance 40mm: Distance 70mm: Dmin(mm): 15 to 25 Dmin(mm): 25 to 40 Dmax(mm): 35 to 55 Dmax(mm): 45 to 60 Area (mm 2 ): 600 to 850 Area (mm 2 ): 1100 to 1700 Area%: 1 to 5 Area
  • an intranasal delivery system optionally comprising an active nasal delivery device as described herein, comprising: a dry powder formulation comprising a plurality of powder particles of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof; and an active nasal delivery device, optionally as described herein, configured to deliver the particles to the turbinates and olfactory region of the nasal cavity of a subject at a single actuation; wherein the system is operably configured to emit a powder plume comprising 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, having one or more of: a plume geometry of: angle: 20 to 35 degrees; width: 25 to 45 mm; a spray pattern of: Distance 40mm: Distance 70mm: Dmin(mm): 15 to 25 Dmin(mm): 15 to 40 Dmax(mm): 20 to 35 Dmax(mm): 35 to 50 Area (mm 2 ): 390 to 460 Area (mm 2 ): 800-1200 Area%: 5 to 15 Area%
  • the powder plume of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof has a plume geometry of: angle: 22 to 35 degrees; width: 27 to 55 mm; or plume geometry of: angle: 22 to 33 degrees; width: 27 to 42 mm; or a plume geometry of: angle: 25 to 30 degrees; width: 29 to 39 mm; or a plume geometry of: angle: 26 to 28 degrees; width: 32 to 35 mm; or a plume geometry of: angle: 27.5 degrees; width: 34.33 mm; or a plume geometry of: angle: 24.4 degrees; width: 30.30 mm; or a plume geometry of: angle: 24.8 degrees; width: 30.76 mm; or a plume geometry of: angle: 27.4 degrees; width: 34.13 mm; or a plume geometry of: angle: 30.5 degrees; width: 38.29 mm; or a plume geometry of: angle: 39.2 degrees; width: 50.35 mm; or a plume geometry of: angle
  • the powder plume of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof has a spray pattern of: Distance 40mm: Distance 70mm: Dmin(mm): 18 to 22 Dmin(mm): 20 to 30 Dmax(mm): 25 to 30 Dmax(mm): 40 to 45 Area (mm 2 ): 400 to 450 Area (mm 2 ): 900-1100 Area%: 7 to 13 Area%: 9 to 15 or Distance 40mm: Distance 70mm: Dmin(mm): 19 to 21 Dmin(mm): 24 to 28 Dmax(mm): 27 to 29 Dmax(mm): 42 to 44 Area (mm 2 ): 425 to 435 Area (mm 2 ): 950-1050 Area%: 8 to 11 Area%: 12 to 14
  • the powder plume of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof has a spray pattern of: Distance 40mm: Distance 70mm: Dmin(mm): 20.43 or 20.17 or 17.79 or 20.09 Dmin(
  • the % particles of equal to or less than 11.7 ⁇ m size of the powder plume of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof is: 0.5 to 5%, 0.6 to 4%, 0.7 to 3%, 0.8 to 2%, 0.9 to 1%.
  • the active nasal delivery has an actuation force of between 30 and 60N. In an embodiment, the actuation force is between 40 and 50N. In an embodiment, the actuation force is 41, 42, 43, 44, 45, 46, 47, 48 or 49N.
  • the actuation force is 36N.
  • the dry powder formulation comprising a plurality of powder particles of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof comprises a crystalline form of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, as described herein.
  • the dry powder formulation comprising a plurality of powder particles of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof has a moisture content of ⁇ 5%, ⁇ 4%, ⁇ 3%, ⁇ 2%, or ⁇ 1%.
  • the moisture content is ⁇ 2%, ⁇ 1.9%, ⁇ 1.8%, ⁇ 1.7%, ⁇ 1.6%, ⁇ 1.5%, ⁇ 1.4%, ⁇ 1.3%, ⁇ 1.2% or ⁇ 1.1%.
  • the dry powder formulation comprising a plurality of powder particles of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, has ⁇ 5%, ⁇ 4%, ⁇ 3%, ⁇ 2%, ⁇ 1%, ⁇ 0.9%, ⁇ 0.8%, ⁇ 0.7%, ⁇ 0.6%, ⁇ 0.5%, ⁇ 0.4%, ⁇ 0.3%, ⁇ 0.2%, ⁇ 0.1%, ⁇ 0.09%, ⁇ 0.08%, ⁇ 0.07%, ⁇ 0.06%, ⁇ 0.05%, ⁇ 0.04%, ⁇ 0.03%, ⁇ 0.02% or ⁇ 0.01% by weight of a hydroxyl impurity.
  • the dry powder formulation comprising a plurality of powder particles of 5-MeO-DMT, or a pharmaceutically acceptable salt thereof, has ⁇ 5%, ⁇ 4%, ⁇ 3%, ⁇ 2%, ⁇ 1%, ⁇ 0.9%, ⁇ 0.8%, ⁇ 0.7%, ⁇ 0.6%, ⁇ 0.5%, ⁇ 0.4%, ⁇ 0.3%, ⁇ 0.2%, ⁇ 0.1%, ⁇ 0.09%, ⁇ 0.08%, ⁇ 0.07%, ⁇ 0.06%, ⁇ 0.05%, ⁇ 0.04%, ⁇ 0.03%, ⁇ 0.02% or ⁇ 0.01% of by weight of any one impurity.
  • the % particles of equal to or less than 11.7 ⁇ m size of the powder plume is determined by Next Generation Impactor and HPLC.
  • the moisture content is determined by Karl Fisher coulometric titration.
  • the plume geometry is analysed using the Proveris SprayVIEW apparatus (or equivalent) in conjunction with the Proveris automated actuation device. In an embodiment, Analysis is performed at one distance (7.0cm).
  • the settings are as follows: Orifice tip distance (cm): 7.0, Frame rate (Hz): 500, Number of images 250, Lens aperture 2.0, Camera position from horizontal (cm): 27.0, Camera height (cm): 8.0, Laser position (cm): 5.2, Laser depth (cm): 5.3, Laser height (cm): 13.2, Actuator position (cm): 7.0, Plume orientation: 0 deg, Palette: Gradient, Arm 1/Arm 2 (%): 20 – 30%, Evacuation time (ms): 1000, Setting time (ms): 1000.
  • the spray pattern is determined using the Proveris SprayVIEW apparatus (or equivalent) in conjunction with the Proveris automated actuation device.
  • analysis is performed at two distances (4.0cm and 7.0cm).
  • the settings are as above for the 7.0cm distance and as follows for the 4.0cm distance (where different from the settings used for 7.0cm): Orifice tip distance (cm): 4.0, Camera position from horizontal (cm): 8.0 and Camera height (cm): 22.
  • the particle size distribution is determined by laser diffraction using a Malvern Mastersizer (or equivalent).
  • the aerodynamic particle size distribution is determined by a method based on USP ⁇ 601>, using the Proveris Sprayview and a Copley Next Generation Impactor (NGI) or equivalent, complying with USP/Ph.Eur.
  • the settings are as follows: Actuation acceleration: 5000mm/s/s, Actuation velocity: 70mm/s, Symmetric: Yes, Initial delay: 0 ms, Hold time: 100 ms, Final delay: 0 ms, Stroke length: 14 mm, One shot is fired into the NGI.
  • a 5-MeO-DMT formulation comprising HPMC, isomalt and methyl cellulose.
  • an extended release formulation of 5-MeO-DMT A spray dried formulation of 50% 5-MeO-DMT benzoate with 3% sorbitol and 47% MC SM-25 was produced.
  • Example 30 5-MeO-DMT buccal formulations
  • Buccal formulations of 5-MeO-DMT have been developed and are characterised below: Composition of formulations (% w/w) Component S01 S12 S26 S27 S28 S29 5-MeO-DMT 3.14 3.14 3.14 1.57 3.14 6.27 benzoate 5-MeO-DMT (corrected for 2.01 2.01 2.01 1.01 2.01 4.02 salt)
  • the formulations were evaluated in
  • Formulation S12 delivered more (p ⁇ 0.05; ⁇ 1.5-fold) 5-MeO-DMT to the receptor solution compared to all other formulations.
  • formulation S29 also had the greatest (p ⁇ 0.05; ⁇ 1.8-fold) peak flux between the tested formulations.
  • formulation S12 delivered more 5-MeO-DMT to the receptor solution as a cumulative percentage (p ⁇ 0.05; 2-fold) and a peak flux percentage (p ⁇ 0.05; 1.8-fold).
  • S29 contains nearly double (4.02 % w/w) API compared to S01, S12, S26, and S28 (2.01 % w/w).
  • the central part of the device may be a dosing capsule to which relevant doses of 5-MeO-DMT in an alcohol solution may be applied and which may then be applied into the filling chamber of the device, where it may be heated via the hot air.
  • the dosing capsules may contain a small disc made of tightly packed stainless-steel wire mesh (called the drip pad or liquid pad).
  • the bottom and the lid of the dosing capsules may have holes, allowing airflow through the dosing capsules.

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Abstract

La présente invention concerne une formulation de poudre sèche de 5-MeO-DMT ou d'un sel pharmaceutiquement acceptable de celui-ci, et un ou plusieurs supports ou excipients pharmaceutiquement acceptables. Les formulations décrites ici peuvent être utilisées pour traiter une maladie ou un état, tel qu'une dépression ou un trouble d'utilisation d'alcool chez un sujet en ayant besoin.
PCT/GB2025/050076 2024-01-18 2025-01-17 Formulations de poudre de 5-méthoxy-n,n-diméthyltryptamine (5-meo-dmt) Pending WO2025153822A1 (fr)

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GB2400703.1 2024-01-18
GBGB2400703.1A GB202400703D0 (en) 2024-01-18 2024-01-18 5-Methoxy-N, N-Dimethyltryptamine (5-MeO-DMT) formulations
US18/607,093 US12246005B2 (en) 2023-06-13 2024-03-15 5-methoxy-n,n-dimethyltryptamine (5-MeO-DMT) formulations
US18/607,093 2024-03-15

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