Mesalamine suppository
View Patent ↗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%. Another embodiment of the invention is a mesalamine rectal suppository comprising from about 850 to about 1150 mg mesalamine and one or more pharmaceutically acceptable excipients, wherein the total weight of the suppository ranges from about 2250 to about 2700 mg. Another embodiment of the invention is a mesalamine rectal suppository comprising from about 400 to about 600 mg mesalamine and one or more pharmaceutically acceptable excipients, wherein the total weight of the suppository ranges from about 870 to about 1715 mg. 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° C. 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° C. and a paddle rotation speed of 125 rpm in 0.2 M phosphate buffer at a pH of 7.5.
1. A mesalamine rectal suppository comprising 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>), 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° 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 450 to about 550 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° C.
4. The mesalamine suppository of claim 1 , wherein the oily or fatty base has an ascending melting point from 33 to 35.5° C.
5. The mesalamine suppository of claim 3 , wherein the oily or fatty base is hard fat.
6. The mesalamine suppository of claim 1 , wherein the drug load ranges from about 39 to about 45%.
7. The mesalamine suppository of claim 6 , wherein the drug load ranges from about 41 to about 43%.
8. 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° C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5.
9. 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° 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 90% by weight of the mesalamine within 30 minutes of dissolution as measured with USP Apparatus #2 at 40° 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. 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.
12. The method of claim 11 , wherein the mesalamine rectal suppository is administered once a day.
13. The method of claim 12 , wherein the mesalamine rectal suppository is administered once a day at bedtime.
14. A mesalamine rectal suppository comprising 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° C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5.
15. The mesalamine rectal suppository of claim 14 , wherein the suppository comprises from about 450 to about 550 mg of mesalamine.
16. The mesalamine rectal suppository of claim 14 , wherein the suppository comprises from about 950 to about 1050 mg of mesalamine.
17. A mesalamine rectal suppository comprising 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° C., a paddle rotation speed of 125 rpm, and 3 sinker turns in 0.2 M phosphate buffer at a pH of 7.5.
18. The suppository of claim 1 , wherein the suppository is a moulded suppository.