Patent EA-004803-B1 (EA)
Title: Rapidly disintegrating methylcellulose tablets and process for preparing same
Inventor: DAGGY BRUCE
IPC: A61K31/716
Filed: 1998-08-21
Abstract: 1. A rapidly disintegrating tablet for oral administration which tablet comprises a compacted mixture of methylcellulose having a viscosity of > 1000 centipoise; and an edible calcium salt selected from dibasic calcium phosphate dihydrate, calcium phosphate anhydrous, tribasic calcium phosphate or mixtures thereof and a binding agent and a wetting agent. 2. The tablet according to Claim 1 wherein the binding agent is selected from PVP, hydroxypropylcellulose, hydroxypropyl methylcellulose, acacia, gelatin, tragacanth, pregelatinized starch or starch. 3. The tablet according to Claim 2 wherein the binding agent is PVP. 4. The tablet according to any one of Claims 1-3 wherein further comprises a disintegrating agent selected from sodium starch glycolate, sodium carboxymethylcellulose, sodium crosscarmellose, carboxymethylcellulose, magnesium-aluminum silicate, veegum, alginates, agar, guar, tragacanth, locust bean, karaya, pectin, or crospovidone. 5. The tablet according to Claim 4 wherein the disintegrating agent is sodium starch glycolate. 6. The tablet according to Claim 5 wherein the sodium starch glycolate is present in an amount of about 3 to about 8 % w/w. 7. The tablet according to Claim 1 wherein the wetting agent is sodium lauryl sulfate. 8. The tablet according to any one of Claims 1-7, which further comprises a lubricating agent. 9. The tablet according to Claim 8 wherein the lubricating agent is magnesium stearate, calcium stearate, sodium stearate, colloid silicon dioxide, powdery silica gel, stearic acid and talc. 10. The tablet according to Claim 9 wherein the lubricating agent is magnesium stearate. 11. The tablet according to any one of Claims 1-10 wherein the methylcellulose has a viscosity of > 2000 centipoises. 12. The tablet according to Claim 11 wherein the methylcellulose has a viscosity of > 3000 centipoises. 13. The tablet according to Claim 12 wherein the methylcellulose has a viscosity of > 4000 centipoises. 14. The tablet according to any one of Claims 1-13 wherein the edible calcium salt is present in a ratio of methylcellulose to calcium from about 2 to about 4:1. 15. The tablet according to any one of Claims 1-12 wherein further comprises additional excipients and diluents in the ratio of: Sodium lauryl sulfate: Tribasic calcium phosphate: Povidone 29K/32: Magnesium stearate include: 0.40:3.5:21.6:6.4:1.0; or Sodium lauryl sulfate: Sodium starch glycolate: Calcium phosphate anhydrous: Povidone 29K/32:Magnesium stearate include:0.40:3.5:21.6:6.4:1.0. 16. The tablet according to any one of Claims 1-15 wherein the methylcellulose is present in an amount of about 450 to about 550 mg. 17. The tablet according to Claim 16 wherein the methylcellulose is present in an amount of about 200 to about 300 mg. 18. A rapidly disintegrating tablet for oral administration which tablet comprises methylcellulose having a viscosity of > 3000 centipoise; dibasic calcium phosphate dihydrate, sodium lauryl sulfate, povidone, sodium starch glycolate and magnesium stearate. 19. A rapidly disintegrating tablet for oral administration which tablet comprises a compacted mixture of methylcellulose having a viscosity of > 1000 centipoise; and an edible calcium salt selected from dibasic calcium phosphate dihydrate, calcium phosphate anhydrous, tribasic calcium phosphate; or mixtures thereof, wherein a ratio of methylcellulose to calcium salt from about 2:1 to about 4:1 and a binding agent and a wetting agent. 20. The tablet according to claim 19 wherein a ratio of methylcellulose to calcium salt is from about 2.6:1 to about 3.1:1. 21. The tablet according to claim 19 wherein a binding agent is selected from PVP, hydroxypropylcellulose, hydroxypropyl methylcellulose, acacia, gelatin, tragacanth, pregelatinized starch or starch. 22. The tablet according to Claim 21 wherein the binding agent is PVP. 23. The tablet according to Claim 22 wherein the PVP is present in an amount of about 4 to about 6.5 % w/w. 24. The tablet according to Claim 24 wherein further comprises a disintegrating agent. 25. The tablet according to Claim 24 wherein the disintegrating agent is selected from sodium starch glycolate, sodium carboxymethylcellulose, sodium crosscarmellose, carboxymethylcellulose, magnesium-aluminum silicate, veegum, alginates, agar, guar, tragacanth, locust bean, karaya, pectin, or crospovidone. 26. The tablet according to Claim 25 wherein the disintegrating agent is sodium starch glycolate. 27. The tablet according to Claim 26 wherein the sodium starch glycolate is present in an amount of about 3 to about 8 % w/w. 28. The tablet according to Claim 19 wherein a wetting agent is sodium lauryl sulfate. 29. The tablet according to Claim 19 which further comprises a lubricating agent. 30. The tablet according to Claim 29 wherein the lubricating agent is magnesium stearate. 31. The tablet according to Claim 19 wherein the methylcellulose has a viscosity of > 2000 centipoises. 32. The tablet according to Claim 31 wherein the methylcellulose has a viscosity of > 3000 centipoises. 33. The tablet according to Claim 32 wherein the methylcellulose has a viscosity of > 4000 centipoises. 34. A process for preparing a tablet formulation according to any one of Claims 1-18 or 19-33, which comprises: a) blending together high viscosity methylcellulose of > 3000 cps, a wetting agent, povidone or sodium starch glycolate, and an edible calcium salt; and b) adding to the mixture of step (a) a PVP aqueous solution, or alternatively spraying the mixture of step (a) with a PVP aqueous solution; and preparing granulates; and c) blending together an extragranular mixture of an edible calcium salt, a wetting agent; a lubricating agent; povidone or sodium starch glycolate or a mixture thereof; and d) compacting the granulates of step (b) with the extragranular mixture of step (c). 35. The process according to Claim 34 wherein the edible calcium salt is dibasic calcium phosphate dihydrate. 36. A process for the manufacture of a pharmaceutical tablet, which process comprises: a) mixing granulates comprising high viscosity methylcellulose of > 3000 cps, a wetting agent, povidone or sodium starch glycolate, an edible calcium salt; and b) blending together an extragranular mixture of an edible calcium salt, a wetting agent; a lubricating agent; povidone or sodium starch glycolate or a mixture thereof; and c) compacting the granulates of step (b) with the granular mixture of step (a); and d) compressing into a tablet. 37. A process for the preparation of granulates which comprises: a) mixing granulates comprising high viscosity methylcellulose of > 3000 cps, a wetting agent, povidone or sodium starch glycolate, an edible calcium salt, wherein the edible calcium salt is selected from dibasic calcium phosphate dihydrate, calcium phosphate anhydrous, tribasic calcium phosphate or mixtures thereof and b) adding to the mixture of step (a) a PVP aqueous solution, or alternatively spraying the mixture of step (a) with a PVP aqueous solution; and preparing granulates. 38. The process according to Claim 37 wherein the granulate is admixed with a second wetting agent, a lubricating agent, and a disintegrant, and compressed to form a tablet. 39. The process according to Claim 38 wherein the disintegrant is selected from sodium starch glycolate, sodium carboxymethylcellulose, sodium crosscarmellose, carboxymethylcellulose, magnesium-aluminum silicate, veegum, alginates, agar, guar, tragacanth, locust bean, karaya, pectin, or crospovidone. 40. The process according to Claim 39 wherein the wetting agent is sodium lauryl sulfate. 41. The process according to Claim 38 wherein the second wetting agent is sodium lauryl sulfate. 42. The process according to Claim 34 wherein the granulate further comprises a diluent. 43. The process according to Claim 42 wherein the diluent is microcrystalline cellulose, corn starch or starch 1500. 44. The process according to Claim 34 wherein the granulate further comprises a disintegrant. 45. The process according to Claim 44 wherein the disintegrant is sodium starch glycolate.