Formulation of indomethacin
The present invention relates to methods for producing particles of indomethacin using dry milling processes as well as compositions comprising indomethacin, medicaments produced using indomethacin in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of indomethacin administered by way of said medicaments.
1. A method of treating pain comprising administering a unit dose of a pharmaceutical composition containing 20 mg of indomethacin, wherein the indomethacin has a median particle size on a volume basis between 25 nm and 1000 nm and wherein the unit dose when tested in vitro by USP Apparatus I (Basket) method of U.S. Pharmacopoeia at 100 rpm at 37° C. in 900 ml of 100 mM citric acid buffer (pH 5.5±0.05) has a dissolution rate of indomethacin such that at least 83%, by weight, is released by 30 minutes.
2. The method of claim 1 , wherein the unit dose has a dissolution rate of indomethacin such that at least 83%, by weight, is released by 20 minutes.
3. The method of claim 1 , wherein the unit dose has a dissolution rate of indomethacin such that at least 83%, by weight, is released by 10 minutes.
4. The method of claim 1 , wherein the unit dose has a dissolution rate of indomethacin such that at least 99%, by weight, is released by 20 minutes.
5. The method of claim 1 , wherein the unit dose has a dissolution rate of indomethacin such that at least 99%, by weight, is released by 30 minutes.
6. The method of claim 1 , wherein the median size of the indomethacin on a particle volume basis is between 500 nm and 25 nm.
7. The method of claim 1 , wherein the unit dose is a hard gelatin capsule.
8. The method of claim 1 , wherein the unit dose further comprises: a binder, a lubricant, and a disintegrant.
9. The method of claim 1 , wherein the unit dose comprises microcrystalline cellulose, croscarmellose sodium, and sodium stearyl fumarate.
10. The method of claim 1 , wherein the D(90) of the indomethacin, on a particle volume basis, is less than 5000 nm.
11. The method of claim 1 , wherein the D(90) of the indomethacin, on a particle volume basis, is less than 3000 nm.
12. The method of claim 6 wherein the mean Tmax for the unit in fasted subjects is 1.1 hrs or less.
13. The method of claim 6 , wherein the pain is acute pain.
14. A method of treating pain comprising administering a unit dose of a pharmaceutical composition containing 40 mg of indomethacin wherein the indomethacin has a median particle size on a volume basis between 25 nm and 1000 nm and wherein the unit dose when tested in vitro by USP Apparatus I (Basket) method of U.S. Pharmacopoeia at 100 rpm at 37° C. in 900 ml of 100 mM citric acid solution buffered to pH 5.5 has a dissolution rate of indomethacin such that at least 66%, by weight, is released by 30 minutes.
15. The method of claim 14 , wherein the unit dose has a dissolution rate of indomethacin such that at least 66%, by weight, is released by 20 minutes.
16. The method of claim 14 , wherein the unit dose has a dissolution rate of indomethacin such that at least 66%, by weight, is released by 10 minutes.
17. The method of claim 14 , wherein the unit dose has a dissolution rate of indomethacin such that at least 93%, by weight, is released by 20 minutes.
18. The method of claim 14 , wherein the unit dose has a dissolution rate of indomethacin such that at least 93%, by weight, is released by 30 minutes.
19. The method of claim 14 , wherein the median size of the indomethacin on a particle volume basis is between 500 nm and 25 nm.
20. The method of claim 14 , wherein the unit dose is a hard gelatin capsule.
21. The method of claim 14 , wherein the unit dose further comprises: a binder, a lubricant, and a disintegrant.
22. The method of claim 14 , wherein the unit dose comprises microcrystalline cellulose, croscarmellose sodium, and sodium stearyl fumarate.
23. The method of claim 14 , wherein the D(90) of the indomethacin, on a particle volume basis, is selected from: less than 5000 nm and less than 5000 nm.
24. The method of claim 14 , wherein the D(90) of the indomethacin, on a particle volume basis, is selected from: less than 5000 nm and less than 3000 nm.
25. The method of claim 14 , wherein the mean Tmax for the unit dose in fasted subjects is 1.25 hrs or less.
26. The method of claim 14 , wherein the pain is acute pain.