Formulation of indomethacin

• US 9,522,135 B2
• Filed: 07/27/2015
• Issued: 12/20/2016
• Est. Priority Date: 04/24/2009
• Status: Active Grant

• Current Assignee: Iceutica Pty Limited (Assertio Holdings, Inc.)
• Original Assignee: Iceutica Pty Limited (Assertio Holdings, Inc.)
• Inventors: Dodd, Aaron, Meiser, Felix, Norret, Marck, Russell, Adrian, Bosch, H. William
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US14/810,240
• Publication Number:
  US 20160022637A1
• Time in Patent Office: 512 Days
• US Class Current: 1/1
• CPC Class Codes: A61J 3/02 into the form of powders pulverising in general B02C
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/513 Organic macromolecular compounds; Dendrimers
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

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.

Claims

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.