Patent EA-004032-B1 (EA)
Title: Quick release pharmaceutical compositions of drug substances
Inventor: BERTELSEN POUL
IPC: A61K9/14
Filed: 1999-09-10
Abstract: 1. A quick release pharmaceutical composition for oral administration comprising a therapeutically and/or prophylactically active substance which is determined by the presence of the following features i) or ii): i) which has a solubility of at the most 0.1 % w/v in 0.1 N hydrochloric acid at room temperature ii) a pKa value of at the most 5.5, and wherein said quick release pharmaceutical composition is characterized by also one features iii) or iv): iii) the quick release pharmaceutical composition is based on the powder comprising a therapeutically and/or prophylactically active substance and having such a particle size that - when the powder is subjected to a sieve analysis - then at least 90% w/w of the particles passes through sieve 180 mum, the powder being contacted with an aqueous medium to form a particulate composition, which has such a particle size that - when the particulate composition is subjected to a sieve analysis - then at least 50% w/w of the particles passes through sieve 180 mum, iv) the quick release pharmaceutical composition being in the form of a particulate composition or being based on a particulate composition which is obtained by contacting a powder comprising the therapeutically and/or prophylactically active substance with an aqueous medium in such a manner that the mean particle size of the particles of the particulate composition is at the most 100% larger than the mean particle size of the powder before contact with the aqueous medium; and wherein said quick release pharmaceutical composition is characterized by the active substance being contacted with an alkaline substance; and wherein said quick release pharmaceutical composition - when tested in accordance with the dissolution method I defined herein employing 0.07 N hydrochloric acid as dissolution medium - releases at least 50% w/w of the active substance within the first 20 min of the test. 2. A composition according to claim 1, wherein the composition - when tested in accordance with the dissolution method I defined herein employing 0.07 N hydrochloric acid as dissolution medium - releases at least 55% w/w of total amount of active substance present in the composition within the first 20 min of the test. 3. A composition according to any one of the preceding claims wherein the solubility of the therapeutically and/or prophylactically active substance in 0.1 N hydrochloric acid at room temperature is at the most 0.05% w/v. 4. A composition according to any one of the preceding claims, wherein the therapeutically and/or prophylactically active substance - when tested by solubility method I described herein - has such a dissolution rate that it allows an amount of at the most 50% w/w of the active substance to be dissolved within the first 20 min of the test. 5. A composition according to any one of the preceding claims, wherein the composition is in the form of a solid composition. 6. A composition according to any one of the preceding claims, wherein the composition is in the form of a particulate composition. 7. A composition according to any one of the preceding claims in the form of a unit dosage form. 8. A composition according to any one of the preceding claims, wherein the aqueous medium comprises water and an organic solvent. 9. A composition according to any one of the preceding claims, wherein the mean particle size of the particles of the particulate composition is at the most 250 mum., whenever appropriate, after contact with an aqueous medium. 10. A composition according to any one of the preceding claims further comprising at least one pharmaceutically acceptable excipient. 11. A composition according to claim 10, wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting of binders, disintegrants, fillers and diluents. 12. A composition according to claim 11, wherein the composition comprises a filler having binding properties. 13. A composition according to claim 12, wherein the filler having binding properties is selected from lactose (such as, e.g., Tabletose (RTM), Pharmatose (RTM)), sugar derivatives (such as, e.g., mannitol, sorbitol), calcium carbonate (CaCO3), tricalcium phosphate (Ca3(PO4)2), calcium hydrogen phosphate (CaHPO4) (such as, e.g., Di-Cafos (RTM), Di-Tab (RTM), Emcompress (RTM) or Pharmacompress (RTM)), and/or mixtures thereof. 14. A composition according to claim 13, wherein the filler having binding properties is calcium hydrogen phosphate. 15. A composition according to any one of claims 12-14, wherein the filler having binding properties as raw material has a mean particle size of at the most 140 mum. 16. A composition according to any one of the preceding claims wherein the alkaline substance is an antacid or an antacid-like substance. 17. A composition according to claim 16, wherein the alkaline substance is an antacid or an antacid-like substance such as, e.g., sodium hydrogen carbonate, magnesium carbonate, magnesium hydroxide or magnesium metasilicate aluminate or mixtures thereof. 18. A composition according to claim 16 or 17, wherein the mean particle size of the antacid-like substance as raw material is at the most 250 mum. 19. A composition according to any one of 10-18 in the form of tablets, capsules or sachets. 20. A composition according to any one of 10-18 in the form of tablets. 21. A composition according to any of claims 19-21, wherein the composition has such a mechanical strength as to enable handling and coating in a conventional coating apparatus. 22. A composition according to claim 21, wherein the composition - when subjected to a crushing strength test in accordance with Ph. Eur. - has a crushing strength of at least 50 N. 23. A composition according to any one of claims 19-22, wherein comprises a filler having binding properties. 24. A composition according to claim 23, wherein the filler having binding properties is selected from lactose (such as, e.g., Tabletose (RTM), Pharmatose (RTM)), sugar derivatives (such as, e.g., mannitol, sorbitol), calcium carbonate (CaCO3), tricalcium phosphate (Ca3(PO4)2), calcium hydrogen phosphate (CaHPO4) (such as, e.g., Di-Cafos (RTM), Di-Tab (RTM), Emcompress (RTM) or Pharmacompress (RTM)), and/or mixtures thereof. 25. A composition according to any one of the preceding claims, wherein the therapeutically and/or prophylactically active substance is a non-steroid antiinflammatory drug substance (NSAID substance). 26. A composition according to any one of the preceding claims, wherein the therapeutically and/or prophylactically active substance is selected from the group consisting of lomoxicam, diclofenac, nimesulide, ibuprofen, piroxicam, piroxicam (betacyclodextrin), naproxen, ketoprofen, tenoxicam, aceclofenac, indometacin, nabumetone, acemetacin, morniflumate, meloxicam, flurbiprofen, tlaprofenic acid, proglumetacin, mefenamic acid, fenbufen, etodolac, tolfenamic acid, sulindac, phenylbutazone, fenoprofen, tolmetin, acetylsalicylic acid, dexibuprofen, paracetamol, and pharmaceutically acceptable salts, complexes and/or prodrugs thereof and mixtures thereof. 27. A composition according to any one of the preceding claims, wherein the therapeutically and/or prophylactically active substance is lomoxicam or a pharmaceutically acceptable salt, complex or prodrug thereof. 28. A composition according to any one of the preceding claims comprising a further active drug substance. 29. A composition according to claim 28, wherein the further active drug substance is selected from the group comprising an antidepressant, an opioid, a prostaglandine analogue (e.g. misoprostol), a glucocorticosteroid, a cytostaticum (e.g. methotrexate), a H2 receptor antagonist (e.g. cimetidine, ranitidine), a proton pump inhibitor (e.g. pantoprazole, omeprazole, lansoprazole) and/or an antacidum. 30. A composition according to claim 28, wherein the further active drug substance is paracetamol, penicillamine, sulfasalazine and/or auranofin. 31. A composition according to any one of the preceding claims in unit dosage form, wherein the unit dosage of the composition comprises from 1 to 32 mg of the therapeutically and/or prophylactically active substance. 32. A composition according to any one of claims 1-30 in unit dosage form, wherein the unit dosage comprises from 1 mg to 1.6 g such as from 1 mg to 1.2 g of the therapeutically and/or prophylactically active substance. 33. A composition according to any one of claims 1-30 in unit dosage form, wherein the unit dosage comprises from 50 mg to 1.1 g of the therapeutically and/or prophylactically active substance. 34. A composition according to any one of claims 1-30 in unit dosage form, wherein a unit dosage comprises from 100 mg to 1.0 g of the therapeutically and/or prophylactically active substance. 35. A composition according to any one of claims 1-30 in unit dosage form, wherein a unit dosage comprises from 200 mg to 900 mg of the therapeutically and/or prophylactically active substance. 36. A composition according to any one of claims 1-30 in unit dosage form, wherein a unit dosage comprises from 300 mg to 800 mg of the therapeutically and/or prophylactically active substance. 37. A composition according to any one of claims 1-30, wherein the therapeutically and/or prophylactically active substance is lomoxicam and a unit dosage of the composition contains 4, 8, 12, 16, 20, 24, 28, 32 or 36 mg of lomoxicam. 38. A composition according to any one of the preceding claims, wherein the water content in the composition is at the most 5% w/w determined by the LOD (loss on drying) method described herein. 39. A composition according to any one of the preceding claims comprising sodium hydrogen carbonate. 40. A composition according to any one of the preceding claims comprising calcium hydrogen phosphate. 41. A composition according to any one of the preceding claims, wherein the composition is coated with a coat which does not substantially retard the release