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
  • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
  • A61K9/0007—Effervescent
• • 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
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• • 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
  • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
  • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
• • 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
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1605—Excipients; Inactive ingredients
  • A61K9/1611—Inorganic compounds
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2009—Inorganic compounds

Definitions

• the present invention relates to pharmaceutical formulations comprising tadalafil that shall be used in the treatment of erectile dysfunction.
• the present invention further relates to effervescent form of tadalafil.
• Tadalafil shown with the Formula I was first disclosed in the application numbered W09519978. In said document, it was disclosed that use of tadalafil is effective in the treatment of erectile dysfunction.
• Tadalafil is available in 5mg, lOmg and 20 mg tablet forms on the market.
• the effervescent formulations comprising tadalafil comprise a composition which is composed of at least two different sweetening agents as the sweetener and the ratio of the first sweetening agent to the second sweetening agent constituting this composition is in the range of 1:5 to 5:1 by weight, bitter taste of said formulations is prevented and they have pleasant taste and since they are easily drinkable, an effective treatment is obtained.
• the first aspect of the present invention is effervescent tadalafil formulations comprising a composition which is composed of at least two different sweetening agents as the sweetener and the ratio of the first sweetening agent: the second sweetening agent constituting the composition is in the range of 1 :5 to 5:1 by weight.
• the subject of the present invention is that an effervescent formulation comprising tadalafil comprises at least two different sweetening agents and the ratio of the first sweetening agent to the second sweetening agent is in the range of 1 :5 to 5:1 by weight.
• Tadalafil comprised in the formulations of the present invention is chemically in the form of its pharmaceutically acceptable salts, hydrates, solvates, esters, enantiomers, diastereomers or combinations thereof, polymorphically in the form of amorphous or crystalline or a combination thereof.
• the characteristic feature of the effervescent formulations of the present invention is that the formulations are in the form of effervescent powder, effervescent tablet and effervescent granule.
• the formulations are preferably in effervescent tablet form.
• the characteristic feature of the effervescent formulations of the present invention is that the ratio of the first sweetening agent: the second sweetening agent constituting the sweetener composition used as the sweetener in the formulations is preferably in the range of 4:1 to 1 :3 by weight, more preferably in the range of 3 : 1 to 1 :2 by weight.
• the characteristic feature of the effervescent formulations of the present invention is that the sweetening agents constituting the sweetener composition in the formulations are selected from a group comprising acesulfame potassium, aspartame, fructose, maltitol, xylitol, saccharin, sodium cyclamate, sucralose, sucrose.
• the characteristic feature of the effervescent formulations of the present invention is that the first sweetening agent constituting the sweetener composition in the formulations is preferably aspartame.
• the characteristic feature of the effervescent formulations of the present invention is that the second sweetening agent constituting the sweetener composition in the formulations is preferably acesulfame potassium.
• a characteristic feature of the effervescent formulations of the present invention is that the ratio of aspartame: acesulfame is preferably in the range of 4:1 to 1:3, more preferably in the range of 3:1 to 1 :2 by weight.
• the characteristic feature of the effervescent formulations comprising tadalafil according to the present invention is to comprise tadalafil in the range of 0.01-10%, preferably in the range of 0.05-5%, more preferably in the range of 0.1 - 3%.
• the ratio of the active agent to the sweetener composition is very high during production, the sweetening agents do not suffice to mask the undesired taste. According to this, the inventors have found that the amount of the sweetener composition to be used is an important parameter which should be adjusted optimally according to the active agent amount.
• the inventors have seen that in the case that the ratio of tadalafil: sweetener composition in the effervescent formulations of the present invention is in the range of 1 :6 to 6:1 by weight, preferably in the range of 1 :4 to 2:1 by weight, bitter taste of the formulations obtained can be masked as required and a solution with a pleasant taste is obtained.
• the ratio of tadalafil: sweetener composition is in the range of 1 :6 to 6:1 by weight, preferably in the range of 1 :4 to 2:1 by weight.
• formulations of the present invention comprise at least one pharmaceutically acceptable excipient along with tadalafil.
• the pharmaceutically acceptable excipients that can be used in the effervescent formulations of the present invention can be selected from a group comprising effervescent acid, effervescent base, binder, filling agent, flavouring agent, coloring agent and anti-foaming agent.
• the effervescent formulations of the present invention comprising tadalafil, characterized in that the flavouring agent to be used is comprised in the range of 0.01-10%, preferably in the range of 0.1-5%, more preferably in the range of 0.5-4% in proportion to total formulation.
• the flavouring agent that can be used in the effervescent formulations of the present invention comprising tadalafil can be selected from menthol, menthane, anethole, methyl salicylate, eucalyptol, cinnamon, 1- methyl acetate, sage, eugenol, oxanon, lemon, orange, strawberry, blackberry or combinations thereof.
• the flavouring agent used according to the present invention is preferably blackberry flavour.
• Another characteristic feature of the effervescent formulation of the present invention is to comprise blackberry flavour in the range of 0.01-10%, preferably in the range of 0.1-5%, more preferably in the range of 0.5-4% in proportion to total formulation.
• the filling agent that can be used in the effervescent formulations of the present invention comprising tadalafil can be selected from a group comprising D-mannitol, xylitol, macrocrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrous, lactose, starch, maltose, dextrin, maltodextrin, magnesium carbonate, talc and combinations thereof.
• the effervescent acid that can be used in the effervescent formulations of the present invention comprising tadalafil can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid and tartaric acid or a combination thereof.
• the effervescent base that can be used in the effervescent formulations of the present invention comprising tadalafil can be selected from a group comprising sodium bicarbonate, sodium citrate dihydrate, sodium hydroxide or combinations thereof.
• the binder that can be used in the effervescent formulations of the present invention comprising tadalafil can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, sorbitol, methyl cellulose, povidone.
• the colouring agent that can be used in the effervescent formulations of the present invention comprising tadalafil can be selected from titanium dioxide, chlorophyll, yellow iron oxide, other synthetic iron oxides, beta-carotene or combinations thereof.
• the antifoaming agent that can be used in the effervescent formulations of the present invention comprising tadalafil can be selected from polydimethylsiloxane, simethicone, other silicones, stearates, alcohols, glycols or combinations thereof.
• effervescent formulations of the present invention comprising tadalafil, characterized in that said formulations comprise active agent in the range of 0.01-10%, filling agent in the range of 1-20%, effervescent acid in the range of 1-80 %, effervescent base in the range of 1- 70%, binder in the range of 1-15%, sweetener composition in the range of 1-15%, flavouring agent in the range of 0.1-10%, colouring agent in the range of 0.01-10%, anti-foaming agent in the range of 0.001-2% in proportion to total formulation.
• the production method for preparation of the effervescent formulation of the present invention comprising tadalafil can be composed of the following steps:
• the effervescent acid, the effervescent base, the binder, the sweetener composition and the filling agent are mixed and granulated with the granulation solution comprising tadalafil.
• the granulation solution used herein can comprise a solvent in addition to tadalafil.
• the granules obtained in the I st step are dried and sieved.
• the flavouring agent, the colouring agent and the anti-foaming agent are added into the granules obtained in the II nd step and the final mixture is obtained.
• the pharmaceutical formulation of the present invention can be used in prevention and treatment of erectile dysfunction.
• Example I Formulation and process for preparation of tadalafil effervescent tablet
• effervescent acid, effervescent base, the binder, aspartame, acesulfame potassium and the filling agent are mixed and granulated with the granulation solution comprising tadalafil.
• the granules obtained in step (a) are dried and sieved.
• the blackberry flavour, the colouring agent and the anti-foaming agent are added into the granules obtained in step (b) and the final mixture is obtained.
• the final mixture obtained is compressed in tablet form or filled into sachets.

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• Health & Medical Sciences (AREA)
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• Epidemiology (AREA)
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• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
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• General Health & Medical Sciences (AREA)
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• Engineering & Computer Science (AREA)
• Inorganic Chemistry (AREA)
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Applications Claiming Priority (6)

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Citations (4)

• 2013
  • 2013-01-18 WO PCT/TR2013/000033 patent/WO2013109221A1/fr not_active Ceased

Patent Citations (4)

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