Claims for Patent: 5,284,662

Summary for Patent: 5,284,662

Title:	Oral osmotic system for slightly soluble active agents
Abstract:	An oral sustained release composition for slightly soluble pharmaceutically active agents comprising a core, a wall around said core, and a bore through said wall connecting said core and the environment outside of said wall; wherein said core comprises a slightly soluble active agent, optionally a crystal habit modifier, at least two osmotic driving agents, at least two different (or two different grades of) hydroxyalkyl celluloses, and optionally lubricants, wetting agents, and carriers; said wall being substantially impermeable to said core components and permeable to water and gastro-intestinal fluids. The composition is most especially adapted for administering carbamazepine.
Inventor(s):	Arun D. Koparkar, Shailesh B. Shah
Assignee:	Novartis Pharmaceuticals Corp
Application Number:	US07/809,026
Patent Claims:	1. An oral osmotic dosage delivery form adapted to deliver carbamazepine comprising(a) core comprisingi. carbamazepine in an amount sufficient to deliver an effective amount thereof over the intended delivery time; ii. an effective amount of a crystal habit modifier for said carbamazepine selected from the group consisting of C1-4 alkyl cellulose, hydroxypropyl cellulose, hydroxypropyl-C1-4 alkyl cellulose, sodium carboxymethyl cellulose, sodium carboxymethyl-C1-4 alkylcellulose, and gelatin; iii. from about 2% to about 15% of the total core weight of a mixture of at least two different hydroxy-C1 -C4 alkyl celluloses which may be hydroxyalkyl celluloses having different alkyl groups or hydroxyalkyl celluloses having the same alkyl groups but are of different grades, wherein the ratio of the higher viscosity hydroxy-C1 -C4 alkyl cellulose to the lower viscosity hydroxy-C1 -C4 alkyl cellulose is about 2:1; iv. a C6 sugar alcohol; v. a mono- or di-saccharide; vi. from 0 to an effective amount of a tabletting lubricant; and vii. from 0 to an effective amount of a wetting agent;said C6 sugar alcohol and said mono- or di-saccharide together comprising from about 15% to about 60% of the core total weight and the weight ratio of the C6 sugar alcohol to said mono- or di saccharide is from about 1:9 to about 9:1; (b) a semi-permeable wall around said core permeable to water or gastric fluid; and (c) a hole through said semipermeable wall connecting said core with the external environment. 2. The delivery form of claim 1 wherein said active agent is present in an amount of from about 100 mg to about 400 mg, based on carbamazepine free base. 3. The delivery form of claim 1 wherein said crystal habit modifier is hydroxypropyl cellulose, said crystal habit modifier being present in an amount of about 9% to about 15% by weight based upon the amount said carbamazepine as free base. 4. The delivery form of claim 1 wherein said hydroxy-C1 -C4 alkyl celluloses are selected from different grades of the same hydroxy-C1 -C4 alkyl cellulose. 5. The delivery form of claim 4 wherein said hydroxy-C1 -C4 alkyl celluloses are selected from hydroxyethylcelluloses. 6. The delivery form of claim 5 wherein said hydroxyethyl cellulose grades are selected from 250H, 250L, 250J, 250E, 250G, 250K, 250M, 250MH, 250H4, and 250HH. 7. The delivery form of claim 1 wherein said C6 sugar alcohol is selected from mannitol, sorbitol and galactitol. 8. The delivery form of claim 7 wherein said C6 sugar alcohol is mannitol. 9. The delivery form of claim 1 wherein said mono- or di-saccharide is selected from glyceraldehyde, threose, erythrose, lyxose, xylose, arabinose, ribose, talose, galactose, idose, gulose, mannose, glucose, altrose, xylulose, tagatose, sorbose, psicose, hamamalose, allose, their corresponding ketoses and deoxy forms, pseudoheptulose, maltose, lactose, sucrose, cellobiose, isomaltose, and mixtures thereof. 10. The delivery form of claim 9 wherein said mono- or di-saccharide is dextrates N.F. 11. The delivery form of claim 1 wherein said tableting lubricant is magnesium stearate. 12. The delivery form of claim 1 wherein said wetting agent is sodium lauryl sulfate. 13. The delivery form of claim 1 further comprising a pharmaceutically acceptable coloring agent which is present in said core. 14. The delivery form of claim 1 wherein said semipermeable wall comprises at least one cellulose acetate, hydroxy-C1 -C4 alkyl, C1 -C4 alkyl cellulose, and a poly C2 -C4 alkylene glycol. 15. The delivery form of claim 14 wherein said polyC2 -C4 alkyleneglycol is polyethyleneglycol 8000. 16. The delivery form of claim 14 wherein said polyC2 -C4 alkyleneglycol is present in an amount of from about 6% to about 10% based on the total permeable wall weight. 17. The delivery form of claim 14 wherein said hydroxy-C1 -C4 alkyl C1 -C4 alkyl cellulose is present in an amount of from about 6% to 10% based on the total semipermeable wall weight. 18. The delivery form of claim 14 wherein said hydroxy-C1 -C4 alkyl C1 -C4 alkyl cellulose in said semipermeable wall is hydroxypropylmethyl cellulose. 19. The delivery form of claim 14 wherein said hydroxy-C1 -C4 alkyl C1 -C4 alkyl cellulose is a grade thereof having a viscosity of about 10-20 cps 20. The delivery form of claim 14 wherein said semipermeable wall comprises at least two different cellulose acetates. 21. The delivery form of claim 20 wherein said cellulose acetates are cellulose acetate 320S NF and cellulose acetate 398-10 NF and the radio of cellulose acetate 320S NF: cellulose acetate 398-10 NF is from about 5:1 to about 8:1. 22. The delivery form of claim 20 wherein the ratio of cellulose acetate 320S NF: cellulose acetate 398-10 NF is from about 6.62:1 to about 6.64:1. 23. The delivery form of claim 1 comprising(a) a core of ______________________________________ carbamazepine 100-400 mg hydroxypropylmethyl cellulose 10-45 mg hydroxyethyl cellulose 250L 5-10 mg hydroxyethyl cellulose 250H 2.5-20 mg Mannitol 25-110 mg Dextrates NF 25-110 mg Sodium Lauryl Sulfate 1-7 mg Magnesium Stearate 1-8 mg Coloring agents 0.5-1.0 mg ______________________________________ in which the hydroxyethyl cellulose 250L:hydroxyethyl cellulose 250H ratio is from 1:4 to 4; and (b) a semipermeable wall of ______________________________________ cellulose acetates 15-20 mg hydroxypropylmethyl cellulose 1.5-2.0 mg polyethyleneglycol 8000 1.5-2.0 mg ______________________________________ and (c) a hole through said semipermeable wall connecting said core and the external environment.