Patent EA-004370-B1 (EA)
Title: Hydrogel-driven drug dosage form
Inventor: APPEL LEAH ELIZABETH
IPC: A61K9/00
Filed: 2000-12-20
Abstract: 1. A controlled release drug dosage form comprising a core and a coating around said core wherein: (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core; (b) said drug-containing composition comprises a drug, a swelling agent, and a drug-entraining agent (c) said coating is water-permeable, water insoluble, and has at least one delivery port therethrough; (d) said swelling agent has a swelling ratio of at least 3.5; and (e) said drug-entraining agent comprises at least 15wt% of said drug-containing composition. 2. A controlled release drug dosage form comprising a core and a coating around said core wherein: (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core; (b) said drug-containing composition comprises a drug and a drug-entraining agent; (c) said water-swellable composition comprises a swelling agent and a tableting aid; (d) said coating is water-permeable, water insoluble, and has at least one delivery port therethrough; (e) the mass ratio of said drug-containing composition to said water-swellable composition has a value of at least 1.5; (f) said water-swellable composition has a swelling ratio of at least 3.5; and (g) said core has a strength following tableting of at least 1361 Kg/cm<2>. 3. A controlled release drug dosage form comprising a core and a coating around said core wherein: (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core; (b) said drug-containing composition comprises a drug and a drug-entraining agent; and (c) said coating is water-permeable, water insoluble, has at least one delivery port therethrough, has a water flux (40/75) of at least 1.0x 10<-3> gm/cm<2>xhr, and a durability of at least 453.6 Kg/cm<2>, wherein controlled release drug dosage form has molecular weight of at least 10,000 daltons; wherein said coating comprises at least 13 wt% of said core mass. 4. A controlled release dosage form comprising a core and a coating around said core wherein: (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core; (b) said drug-containing composition comprises a drug and a drug-entraining agent; and (c) said coating is water-permeable, water insoluble, has at least one delivery port therethrough, is porous and is formed from a substantially homogeneous solution comprising a solvent, a cellulosic polymer, and a non-solvent, wherein controlled release drug dosage form has molecular weight of at least 10,000 daltons; wherein said release dosage form comprises at least 20 wt% of said drug-containing composition. 5. A controlled release drug dosage form comprising a core and a coating around said core wherein: (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core; (b) said drug-containing composition comprises a drug, a drug-entraining agent, and a fluidizing agent, said fluidizing agent having a solubility of at least 30 mg/mL and comprising at least 10 wt% of said drug-containing composition; and (c) said coating is water-permeable, water insoluble, and has at least one delivery port therethrough, wherein controlled release drug dosage form has molecular weight of at least 20,000 daltons; 6. A controlled release dosage form comprising a core and a coating around said core wherein: (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core; (b) said drug-containing composition comprises a drug, a solubilizer, and a drug-entraining agent; and (c) said coating is water-permeable, water insoluble, and has at least one delivery port therethrough. 7. The dosage form of claim 1 wherein said swelling agent is an ionic swelling agent selected from the group consisting of sodium croscarmellose and sodium starch glycolate. 8. The dosage form of any one of claims 2-6 wherein said drug-containing composition further comprises an ionic swelling agent selected from the group consisting of sodium croscarmellose and sodium starch glycolate. 9. The dosage form of any one of claims 1-5 wherein said core includes a solubilizer and said drugcontaining composition further includes a concentration enhancing polymer. 10. The dosage form of claim 6 wherein said drug-containing composition further includes a concentration-enhancing polymer. 11. The dosage form of any one of claims 1-5 wherein said drug-containing composition further comprises a solubilizer. 12. The dosage form of claim 11 wherein said solubilizer is an organic acid, and said drug has enhanced solubility in the presence of said organic acid. 13. The dosage form of claim 6 wherein said solubilizer is an organic acid, and said drug has enhanced solubility in the presence of said organic acid. 14. The dosage form of any one of claims 1-4 and 6 wherein said drug-containing composition further comprises a fluidizing agent. 15. The dosage form of claim 14 wherein said fluidizing agent is selected from the group consisting of an organic acid and a sugar. 16. The dosage form of claim 5 wherein said fluidizing agent is selected from the group consisting of an organic acid and a sugar. 17. The dosage form of claim 2 wherein said swelling agent of said water-swellable composition is selected from the group consisting of sodium starch glycolate and sodium croscarmellose. 18. The dosage form of any one of claims 1 and 3-6 wherein said water-swellable composition further comprises a swelling agent selected from the group consisting of sodium starch glycolate and sodium croscarmellose. 19. The dosage form of any one of claims 1, 3, 4, 5 or 6 wherein said water-swellable composition has a swelling ratio of at least 3.5. 20. The dosage form of any of claims 1, 3, 4, 5 or 6 wherein the mass ratio of said drug-containing composition to said water-swellable composition is at least 1.5. 21. The dosage form of any one of claims 1-6 wherein said drug has a maximum solubility of 20 mg/mL in aqueous solution that has a pH between 1 and 8. 22. The dosage form of any of claims 1, 2, 4, 5 or 6 wherein said coating has a water flux (40/75) of at least 1.0 x 10<-3>g/cm<2>xhr. 23. The dosage form of any one of claims 1-3 and 5-6 wherein said coating is porous and is formed from a homogeneous solution comprising a solvent, a hydrophilic cellulosic polymer, and a non-solvent. 24. The dosage form of any one of claims 1-6 wherein said coating is porous with a dry-state density of less than 0.9 times that of the same coating material in nonporous form. 25. The dosage form of any one of claims 1, 2, 3, 4 or 6 wherein, following introduction of said dosage form to a use environment, at least about 70 wt% of said drug is released to said use environment within about 12 hours. 26. The dosage form of any one of claims 1-6 wherein said drug-containing composition further includes a concentration-enhancing polymer selected from the group consisting of (a) ionizable cellulosic polymers; (b) non-ionizable cellulosic polymers; and (c) vinyl polymers and copolymers having substituents selected from the group consisting of hydroxyl, alkylacyloxy, and cyclicamido. 27. The dosage form of any of claims 1 to 6 wherein said low-solubility drug is in the form of an amorphous dispersion and said amorphous dispersion is a solid dispersion of a low-solubility drug in a concentration-enhancing polymer. 28. A controlled release dosage form comprising a core and a coating around said core wherein: (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core; (b) said drug-containing composition comprises a low-solubility drug and a drug-entraining agent; and (c) said coating is water-permeable, water insoluble, and has at least one delivery port therethrough; and (d) wherein said drug-containing composition further comprises a concentration-enhancing polymer and said concentration-enhancing polymer has molecular weight of at least 10,000 daltons and said drug is in the form of a solid dispersion. 29. A method for treating a disorder, comprising administering to a mammal in need of such treatment, including a human patient, a therapeutically effective amount of drug in a dosage form as defined in claim 1. 30. A method for treating a disorder, comprising administering to a mammal in need of such treatment, including a human patient, a therapeutically effective amount of drug in a dosage form as defined in claim 2. 31. A method for treating a disorder, comprising administering to a mammal in need of such treatment, including a human patient, a therapeutically effective amount of drug in a dosage form as defined in claim 3. 32. A method for treating a disorder, comprising administering to a mammal in need of such treatment, including a human patient, a therapeutically effective amount of drug in a dosage form as defined in claim 4. 33. A method for treating a disorder, comprising administering to a mammal in need of such treatment, including a human patient, a therapeutically effective amount of drug in a dosage form as defined in claim 5. 34. A method for treating a disorder, comprising administering to a mammal in need of such treatment, including a human patient, a therapeutically effective amount of drug in a dosage form as defined in claim 6. 35. A method for treating a disorder, comprising administering to a mammal in need of such treatment, including a human patient, a therapeutically effective amount of drug in a dosage form as defined in claim 28. 36. A controlled release drug dosage form according to claims 1-28 in which said drug is an antiimpotence agent. 37. A controlled release drug dosage form according to claims 1-28 in which said