Patent EA-003663-B1 (EA)
Title: Rapidly disintegrating methylcellulose tablets
Inventor: DAGGY BRUCE
IPC: A61K31/716
Filed: 1998-08-21
Abstract: 1. A rapidly disintegrating tablet for oral administration which tablet comprises an intragranular and extragranular component, intragranular component contains methylcellulose having a viscosity of > 1000 centipoises; a binding agent; diluent, selected from a group consisting of microcrystalline cellulose, corn starch, and, optionally, intragranular disintegrating agent; and extragranular agent comprises wetting agent, lubricating agent, and, optionally extragranular disintegrating agent; and is present in a ratio of methylcellulose to wetting agent from 60:1 to 170:1 w/w, methylcellulose to binding agent from 8:1 to 22:1 w/w; and methylcellulose to lubricating agent from 50:1 to 150:1 w/w. 2. The tablet according to Claim 1, which further comprises a extragranular disintegrating agent. 3. The tablet according to Claim 2 wherein the disintegrating agent is sodium starch glycolate. 4. The tablet according to Claim 3 wherein the sodium starch glycolate is present in an amount of about 3 to about 7% w/w. 5. The tablet according to Claims 1 or 2 wherein the wetting agent is sodium lauryl sulfate. 6. The tablet according to Claims 1 or 2 wherein the binding agent is PVP. 7. The tablet according to Claims 1 or 2, which further comprises a lubricating agent. 8. The tablet according to Claim 7 wherein the lubricating agent is magnesium stearate. 9. The tablet according to Claim 1 wherein the methylcellulose has a viscosity of >2000 centipoises. 10. The tablet according to Claim 9 wherein the methylcellulose has a viscosity of >3000 centipoises. 11. The tablet according to Claim 10 wherein the methylcellulose has a viscosity of >4000 centipoises. 12. The tablet according to Claim 1 wherein diluent is microcrystalline cellulose and is present in amount giving a ratio of methylcellulose to microcrystalline cellulose from about 2.1 to about 14:1. 13. The tablet according to Claim 1 wherein diluent is corn starch, and is present in amount giving a ratio of methylcellulose to corn starch from about 7.5 to about 15:1. 14. The tablet according to Claim 1 wherein diluent is pregelatinized starch, and is present in amount giving a ratio of methylcellulose to starch from about 2.0 to about 5.0:1. 15. The tablet according to Claim 1 or 12, wherein microcrystalline cellulose has a particles size from 50 to 180 micron. 16. The tablet according to Claim 1, where methylcellulose is present in amount of from about 450 to about 550 mg. 17. The tablet according to Claim 1, where methylcellulose is present in amount of from about 200 to about 300 mg. 18. The tablet according to Claim 1 which further comprises additional excipients and diluents: Sodium lauryl sulfate: sodium starch glycolate: microcrystalline cellulose: Povidone 29K/32: Magnesium stearate in ratio: 0.35-0.46:3.05-6.17:4.38-27.13:4.38-6.66:0.76-1.14; or Sodium lauryl sulfate: sodium starch glycolate: microcrystalline cellulose: Povidone 29K/32: Magnesium stearate in ratio: 0.35-0.46:4.9-6.17:9.21-25.53:4.38-6.66:0.76-1.14; or Sodium lauryl sulfate: sodium starch glycolate: microcrystalline cellulose: Povidone 29K/32: Magnesium stearate in ratio: 0.38-0.42:19.27-25.53:5.99-6.66:0.04; or Sodium lauryl sulfate: sodium starch glycolate: microcrystalline cellulose: Povidone 29K/32: Magnesium stearate in ratio: 0.36-0.38:3.66-7.07:24.05-25.89:4.35-4.68:0.88-0.95. 19. The tablet according to Claim 1, wherein the components of extragranular mixture comprises a microcrystalline cellulose, Sodium lauryl sulfate, Magnesium stearate. 20. The tablet according to Claim 1, wherein the components of extragranular mixture comprises starch, Sodium lauryl sulfate, Sodium starch glycolate and Magnesium stearate. 21. The tablet according to Claim 1 wherein the intragranular 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 1 wherein the optionally disintegrating agent is sodium starch glycolate, sodium carboxymethylcellulose, sodium crosscarmelose, carboxymethylcellulose, veegum, alginates, agar, guar, tragacanth, locust bean, karaya, pectin, or crospovidone. 24. The tablet according to Claim 1, which further comprises Sodium starch glycolate as extragranular component. 25. A rapidly disintegrating tablet for oral administration, which contains intragranular component, comprising methylcellulose with viscosity of > 3000 centipoises. 26. A process for preparing a tablet formulation which comprises compacting a mixture of a) blending together of methylcellulose of high viscosity methylcellulose of > 3000cps; a diluent, selected from group consisting of group consisting of microcrystalline cellulose, corn starch, pregelatinized starch and their mixtures, and optionally, disintegrating agent, to form intragranular mixture; 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 a wetting agent; a lubricating agent; and optionally disintegrating agent or their mixtures, with granulates of step (b) 27. A process for preparing a tablet, comprising compressing of formulation of tablet, obtained by blending of granulates of step (b) according to claim 21 with extragranular mixture as said in step (c) according to Claim 21 with obtaining a tablet. 28. A process of Claim 26, where the extragranular mixture contains microcrystalline cellulose, Sodium lauryl sulfate and Magnesium stearate. 29. A process of Claim 26, where the extragranular mixture contains a starch, Sodium lauryl sulfate, sodium starch glycolate and Magnesium stearate. 30. A process for the manufacture of a pharmaceutical tablet, which process comprises mixing a) granulates comprising high viscosity methylcellulose of > 3000cps, diluent, selected from group consisting of microcrystalline cellulose, corn starch, pregelatinized starch and their mixtures, and optionally, intragranular disintegrating agent and/or a wetting agent; with b) An extragranular disintegrating agent and wetting agent and, optionally extragranular lubricating agent; and c) Compressing into a tablet. 31. The process according to Claim 26 wherein the extragranular mixture further comprises sodium starch glycolate. 32. The process according to Claim 31 wherein the sodium starch glycolate is present in an amount of about 3 to about 7% w/w. 33. The process according to Claim 26, wherein the diluent at step (a) is microcrystalline cellulose. 34. The process according to Claim 26 wherein diluent of step (a) is microcrystalline cellulose, and is present in amount giving a ratio of methylcellulose to microcrystalline cellulose from about 2.1 to about 14:1. 35. The process according to Claim 26 wherein diluent of step (a) is corn starch, and is present in amount giving a ratio of methylcellulose to corn starch from about 7.5 to about 15:1. 36. The process according to Claim 26 wherein diluent of step (a) is pregelatinized starch, and is present in amount giving a ratio of methylcellulose to pregelatinized starch from about 2.0 to about 5.0:1. 37. A method of treatment of constipation of human in need, comprising an administration to said human of effective quantity of pharmaceutical composition in form of rapidly disintegrating tablet for oral administration, wherein said tablet containing intragranular component, comprising methylcellulose, with viscosity of > 1000 centipoises, binding agent; diluent, selected from the group consisting of microcrystalline cellulose, corn starch, pregelatinized starch, and their mixtures; a wetting agent; and, optionally, intragranular disintegrating agent; and extragranular component, containing a wetting agent, lubricant and, optionally extragranular disintegrating agent; and where the ratio, in percent of weight, of methylcellulose to wetting agent is 60:1, to 170:1; methylcellulose to binding agent - from 8:1 to 22:1; and methylcellulose to lubricant - from 50:1 to 150:1.