Claims for Patent: 8,436,051

Summary for Patent: 8,436,051

Title:	Mesalamine suppository
Abstract:	The present invention relates to a mesalamine rectal suppository designed to provide improved comfort of use. One embodiment of the invention is a mesalamine rectal suppository comprising mesalamine and one or more pharmaceutically acceptable excipients, wherein the drug load of the suppository ranges from 35% to 50%. Yet another embodiment of the invention is a mesalamine rectal suppository comprising mesalamine having a tap density ranging from about 600 to about 800 g/L (as measured by USP <616>) and a hard fat having an ascending melting point of 32 to 35.5.degree. C. Yet another embodiment is a mesalamine rectal suppository comprising mesalamine particles and one or more pharmaceutically acceptable excipients, where the mesalamine particles have a surface area of from about 0.1 m.sup.2/g to about 2.8 m.sup.2/g (e.g., from about 0.1 m.sup.2/g to about 1.3 m.sup.2/g). Methods of preparing and methods of treatment with mesalamine suppositories are also provided. The invention further provides a method of determining a dissolution parameter (such as dissolution rate) of a mesalamine rectal suppository, such as a 1 g mesalamine suppository, by measuring its dissolution with USP Apparatus #2 at 40.degree. C. and a paddle rotation speed of 125 rpm in 0.2 M phosphate buffer at a pH of 7.5.
Inventor(s):	Gauthier; Carl (Quebec, CA), Dumoulin; Yves (Quebec, CA), Powell; David (Loudon, TN), Moreau; Hugues (Luce, FR)
Assignee:	Aptalis Pharma Canada Inc. (Mont-Saint-Hilaire, Quebec, CA)
Application Number:	12/639,645
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,436,051
Patent Claims:	1. A mesalamine rectal suppository comprising from about 400 to about 1600 mg mesalamine and an oily or fatty base, wherein the mesalamine has a tap density ranging from about 600 to about 800 g/L (as measured by USP <616>), wherein the suppository has a drug load ranging from 35% to 50%, and the suppository releases at least about 75% by weight of the mesalamine within 2 hours of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 2. The mesalamine suppository of claim 1, wherein the suppository comprises from about 1450 to about 1550 mg of mesalamine. 3. The mesalamine suppository of claim 1, wherein the oily or fatty base has an ascending melting point ranging from 32 to 33.5.degree. C. 4. The mesalamine suppository of claim 1, wherein the oily or fatty base has an ascending melting point ranging from 33 to 35.5.degree. C. 5. The mesalamine suppository of claim 1, wherein the oily or fatty base is hard fat. 6. The mesalamine suppository of claim 3, wherein the oily or fatty base is hard fat. 7. The mesalamine suppository of claim 1, wherein the drug load ranges from about 39 to about 45%. 8. The mesalamine suppository of claim 7, wherein the drug load ranges from about 41 to about 43%. 9. The mesalamine suppository of claim 1, wherein the suppository releases at least about 80% by weight of the mesalamine within 2 hours of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 10. The mesalamine suppository of claim 1, wherein the suppository releases at least about 80% by weight of the mesalamine within 1 hour of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 11. The mesalamine suppository of claim 1, wherein the suppository releases at least 90% by weight of the mesalamine within 30 minutes of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 12. A method of treating active ulcerative proctitis in a patient in need thereof comprising administering the mesalamine rectal suppository of claim 1 to the patient. 13. The method of claim 12, wherein the mesalamine rectal suppository is administered once a day. 14. The method of claim 13, wherein the mesalamine rectal suppository is administered once a day at bedtime. 15. A mesalamine rectal suppository comprising from about 950 to about 1600 mg mesalamine and an oily or fatty base, wherein the mesalamine has a tap density ranging from about 600 to about 800 g/L (as measured by USP <616>), and the suppository releases at least about 75% by weight of the mesalamine within 2 hours of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 16. The mesalamine rectal suppository of claim 15, wherein the suppository comprises from about 1450 to about 1550 mg of mesalamine. 17. The mesalamine rectal suppository of claim 15, wherein the suppository comprises about 1500 mg of mesalamine. 18. A mesalamine rectal suppository comprising from about 950 to about 1600 mg mesalamine and an oily or fatty base, wherein the suppository has a drug load ranging from 35% to 46%, and the suppository releases at least about 75% by weight of the mesalamine within 2 hours of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 19. A mesalamine rectal suppository comprising mesalamine particles and an oily or fatty base, wherein the mesalamine particles have a surface area of from about 0.1 m.sup.2/g to about 2.8 m.sup.2/g, the suppository has a drug load ranging from 35% to 50%, and the suppository releases at least about 85% by weight of the mesalamine within 1 hour of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 20. The mesalamine rectal suppository of claim 19, wherein the mesalamine particles have a surface area of from about 0.1 m.sup.2/g to about 1.3 m.sup.2/g. 21. The mesalamine rectal suppository of claim 19, wherein the suppository comprises about 500 mg mesalamine. 22. The mesalamine rectal suppository of claim 19, wherein the suppository comprises about 1 g mesalamine. 23. The mesalamine rectal suppository of claim 19, wherein the suppository comprises about 1.5 g mesalamine. 24. The mesalamine suppository of claim 19, wherein the oily or fatty base has an ascending melting point ranging from 32 to 33.5.degree. C. 25. The mesalamine suppository of claim 19, wherein the oily or fatty base has an ascending melting point ranging from 33 to 35.5.degree. C. 26. The mesalamine suppository of claim 18, the oily or fatty base is hard fat. 27. The mesalamine suppository of claim 19, the oily or fatty base is hard fat. 28. The mesalamine suppository of claim 19, wherein the drug load ranges from about 39 to about 45%. 29. The mesalamine suppository of claim 28, wherein the drug load ranges from about 41 to about 43%. 30. The mesalamine suppository of claim 19, wherein the suppository releases at least 90% by weight of the mesalamine within 30 minutes of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 31. The mesalamine rectal suppository of claim 20, wherein the suppository releases (a) at least 41.4% (w/w) of the mesalamine after 20 minutes of dissolution, and (b) at least 62.3% (w/w) of the mesalamine after 30 minutes of dissolution, as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 32. A method of treating active ulcerative proctitis in a patient in need thereof comprising administering the mesalamine rectal suppository of claim 19 to the patient. 33. A mesalamine rectal suppository comprising mesalamine particles and an oily or fatty base, wherein the mesalamine particles have a surface area of from about 0.1 m.sup.2/g to about 2.8 m.sup.2/g, the suppository has a drug load ranging from 35% to 50%, and the suppository releases (a) between 15.0% and 95.1% (w/w) of the mesalamine after 10 minutes of dissolution, (b) at least 27.9% (w/w) of the mesalamine after 20 minutes of dissolution, and (c) at least 32.5% (w/w) of the mesalamine after 30 minutes of dissolution, as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 34. The mesalamine rectal suppository of claim 33, wherein the surface area of the mesalamine particles ranges from about 1.3 m.sup.2/g to about 2.8 m.sup.2/g. 35. The mesalamine rectal suppository of claim 34, wherein the suppository releases (a) between 19.1% and 40.3% (w/w) of the mesalamine after 10 minutes of dissolution, (b) between 27.9% and 70.7% (w/w) of the mesalamine after 20 minutes of dissolution, and (c) between 32.5% and 94.8% (w/w) of the mesalamine after 30 minutes of dissolution, as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 36. A mesalamine rectal suppository comprising mesalamine particles and an oily or fatty base, wherein the mesalamine particles have a surface area of from about 0.1 m.sup.2/g to about 2.8 m.sup.2/g and a tap density ranging from about 600 to about 800 g/L (as measured by USP <616>), and the suppository releases at least about 85% by weight of the mesalamine within 1 hour of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 37. The mesalamine rectal suppository of claim 36, wherein the surface area of the mesalamine particles ranges from about 0.1 m.sup.2/g to about 1.3 m.sup.2/g. 38. The mesalamine rectal suppository of claim 36, wherein the suppository has a drug load ranging from 35% to 50%. 39. The mesalamine rectal suppository of claim 36, wherein the suppository comprises about 500 mg mesalamine. 40. The mesalamine rectal suppository of claim 36, wherein the suppository comprises about 1 g mesalamine. 41. The mesalamine rectal suppository of claim 36, wherein the suppository comprises about 1.5 g mesalamine. 42. A mesalamine rectal suppository comprising from 1.1 to 2.5 g mesalamine particles and an oily or fatty base, wherein the mesalamine particles have (i) a surface area of from about 0.1 m.sup.2/g to about 2.8 m.sup.2/g, (ii) a tap density ranging from about 600 to about 800 g/L (as measured by USP <616>), or (iii) both, and the suppository releases at least about 85% by weight of the mesalamine within 1 hour of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 43. A mesalamine rectal suppository comprising mesalamine particles and an oily or fatty base, wherein the mesalamine particles have (i) a surface area of from about 0.1 m.sup.2/g to about 2.8 m.sup.2/g, (ii) a tap density ranging from about 600 to about 800 g/L (as measured by USP <616>), or (iii) both, the suppository having a drug load ranging from 25% to 50%, and the suppository releases at least about 85% by weight of the mesalamine within 1 hour of dissolution as measured with USP Apparatus #2 at 40.degree. C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5. 44. The mesalamine rectal suppository of claim 43, wherein the suppository comprises about 400 to about 800 mg mesalamine. 45. The mesalamine rectal suppository of claim 1, wherein the suppository is a moulded suppository. 46. The mesalamine rectal suppository of claim 15, wherein the suppository is a moulded suppository. 47. The mesalamine rectal suppository of claim 18, wherein the suppository is a moulded suppository. 48. The mesalamine rectal suppository of claim 19, wherein the suppository is a moulded suppository. 49. The mesalamine rectal suppository of claim 33, wherein the suppository is a moulded suppository. 50. The mesalamine rectal suppository of claim 36, wherein the suppository is a moulded suppository. 51. The mesalamine rectal suppository of claim 42, wherein the suppository is a moulded suppository. 52. The mesalamine rectal suppository of claim 43, wherein the suppository is a moulded suppository.