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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
  • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
• • 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
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
  • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

• the present invention relates to formulations comprising dexibuprofen used in symptomatic treatment for prophylaxis of pain and inflammation associated with osteoarthritis, in symptomatic treatment of primary dysmenorrhea, in symptomatic treatment of all mild to moderate musculoskeletal system or dental pains.
• Said formulations are characterized in being in film coated tablet form.
• Dexibuprofen was first disclosed in the patent numbered US3385886. It was disclosed in said document that dexibuprofen is used in the treatment of painful joint inflammations seen in rheumatoid arthritis, Still's disease and osteoarthritis; various non-specific infection or rheumatic conditions affecting fibromuscular tissues and connective tissues; in treatment of rheumatic fever and sequelae.
• Dexibuprofen is in 400 mg tablet form on the market.
• Dexibuprofen is an anti-inflammatory drug having low melting point and low solubility.
• low soluble formulations comprising dexibuprofen are prepared in tablet form, it is seen that they hardly and slowly disperse in body liquid when taken in body. Failure of tablet formulations comprising dexibuprofen to disperse in body fast and easily during use leads to results such as low absorption, low drug plasma level and thus low therapeutic activity.
• the inventors have surprisingly seen that the formulations formulated in film tablet form and comprising dexibuprofen disperse homogeneously and fast in body and an efficient treatment is obtained due to high absorption they provide in the case that said formulations comprise cellulose-based diluent, cellulose-based disintegrant and cellulose-based binder and the ratio of these excipients to each other by weight is in the range of 85:2:0.5 to 10:0.5:2 respectively.
• the first element of the invention is formulations comprising dexibuprofen and formulated in film tablet form which are characterized in that said formulations comprise cellulose-based diluent, cellulose-based disintegrant and cellulose-based binder and the ratio of these excipients to each other by weight is in the range of 85:2:0.5 to 10:0.5:2 respectively.
• the present invention relates to formulations comprising dexibuprofen and formulated in film coated tablet form characterized in that said formulations comprise cellulose-based diluent, cellulose-based disintegrant and cellulose-based binder and the ratio of these excipients to each other by weight is in the range of 85:2:0.5 to 10:0.5:2 respectively.
• the active agent dexibuprofen comprised in the formulations of the present invention can be in the form of its solvates, hydrates, esters, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and/or combinations thereof.
• a characteristic of the formulations of the present invention is that said formulations comprise the active agent dexibuprofenin the range of 20-80%, preferably in the range of 30-70%.
• Another characteristic feature of the formulations of the present invention is that the ratio of the cellulose-based diluent, disintegrant and binder to each other by weight is in the range of 40: 1 :0.5 to 20: 1 :2 respectively.
• the diluent in the present invention can be selected from a group comprising microcrystalline cellulose, silicified microcrystalline, cellulose acetate, modified cellulose and/or combinations thereof.
• microcrystalline cellulose can be used as diluent in the formulations of the present invention.
• the disintegrant in the formulation can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, methyl cellulose or combinations thereof.
• carboxymethyl cellulose calcium can be used as disintegrant in the formulations of the present invention.
• the binder in the formulation can be selected form a group comprising ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, hydroxypropyl methyl cellulose or a combination thereof.
• hydroxypropyl methyl cellulose can be used as binder in the formulations prepared according to the present invention.
• the ratio of microcrystalline cellulose, carboxymethyl cellulose calcium and hydroxypropyl methyl cellulose to each other by weight is preferably in the range of 85:2:0.5 to 10:0.5:2, more preferably in the range of 40: 1 :0.5 to 20: 1 :2 respectively.
• formulations of the present invention comprise at least one pharmaceutically acceptable excipient in addition to the active agent dexibuprofen, diluent, disintegrant and binder.
• the excipients that can be used in the formulations of the present invention can be selected from a group comprising anti-adhesive agent, glidant, lubricant, optionally coating agent or combinations thereof.
• the formulations of the present invention do not adhere to the punches during preparation and they have proper flow characteristics in the case that they comprise an anti-adhesive agent in the range of 0.01% to 2%, preferably in the range of 0.05% to 1% and a glidant in the range of 0.5% to 5%, preferably in the range of 0.8% to 4% in proportion to total weight.
• the formulation comprises an anti-adhesive agent in the range of 0.01 % to 2%, preferably in the range of 0.05% to 1% and a glidant in the range of 0.5% to 5%, preferably in the range of 0.8% to 4% in proportion to total weight.
• the anti-adhesive agent to be used in the formulations of the present invention can be selected from a group comprising talc, stearates, colloidal silicon dioxide, sodium sulfate, starch, leucine or a combination thereof.
• the glidant to be used in the formulations of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate or a combination thereof.
• the lubricant to be used in the formulations of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
• the film coating agent in the formulations of the present invention can be selected from a group comprising titanium dioxide, polyvinyl alcohol, polyethylene glycol, talc, lecithin or a combination thereof.
• the film coating agent marketed under the name Opadry Yellow® can be used.
• formulations of the present invention comprises at least another active agent in addition to dexibuprofen used as the active agent.
• the second active agent that can be used in the formulations of the present invention can be selected from antibiotic, antiseptic, antipyretic, anti-inflammatory, muscle relaxant, analgesic, non-steroid anti-inflammatory, sympathomimetic drugs or combinations thereof.
• the formulations of the present invention can preferably comprise an analgesic and/or antipyretic drug, more preferably paracetamol as the second active agent in addition to dexibuprofen used as the active agent.
• the formulations of the present invention can preferably comprise a sympathomimetic drug, more preferably pseudoephedrine as the second active agent in addition to dexibuprofen used as the active agent.
• the formulations prepared according to the present invention can comprise 20-80% dexibuprofen, 10-50% diluent, 0.5-3% disintegrant, 1-3.5% binder, 0.1-2% lubricant, 1-5% coating agent in proportion to total weight of unit dose.
• dexibuprofen and the diluent are mixed, the mixture is granulated with a granulation solution comprising binder.
• the obtained granules are dried, sieved and mixed with the disintegrant, anti-adhesive agent and glidant.
• This mixture is lubricated with the lubricant and then tablet compression is started.
• the tablets compressed are coated with the coating solution comprising coating agent.
• the dexibuprofen formulations of the present invention can be used in symptomatic treatment for prophylaxis of pain and inflammation associated with osteoarthritis, in symptomatic treatment of primary dysmenorrhea, in symptomatic treatment of all mild to moderate musculoskeletal system or dental pains.
• the formulation given below is prepared by wet granulation method.
• Dexibuprofen and diluent mixture is granulated with a granulation solution comprising the binder.
• the obtained granules are dried, sieved and mixed with the disintegrant, anti-adhesive agent and glidant.
• This mixture is lubricated with the lubricant and then tablet compression is started.
• the compressed tablets are coated with a coating solution comprising coating agent.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)

Applications Claiming Priority (4)

Publications (1)

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Citations (5)

• 2013
  • 2013-04-03 WO PCT/TR2013/000110 patent/WO2013154511A1/fr not_active Ceased

Patent Citations (5)

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