Formulation of indomethacin

• US 9,095,496 B2
• Filed: 01/06/2014
• Issued: 08/04/2015
• 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:
  US14/148,635
• Publication Number:
  US 20140194487A1
• Time in Patent Office: 575 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 for producing a solid unit dosage pharmaceutical composition comprising indomethacin, comprising:

dry milling a composition comprising indomethacin, a millable grinding compound and a facilitating agent in a mill containing a plurality of milling bodies for a time period sufficient to produce a composition comprising particles of indomethacin having a median particle size, on a particle volume basis, between 3,000 nm and 25 nm; and

processing the composition comprising particles of indomethacin into a solid unit dosage pharmaceutical composition containing 20 mg of indomethacin, wherein the solid unit dosage pharmaceutical composition, 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 75 minutes.

2. The method of claim 1, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 83%, by weight, is released by 60 minutes.

3. The method of claim 1, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 83%, by weight, is released by 45 minutes.

4. The method of claim 1, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 83%, by weight, is released by 30 minutes.

5. The method of claim 1, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 83%, by weight, is released by 20 minutes.

6. The method of claim 1, wherein the particles of indomethacin have a median particle size, on a volume average basis, between 25 nm and 1000 nm.

7. The method of claim 1 wherein the particles of indomethacin have a median particle size, on a volume average basis, between 25 nm and 700 nm.

8. The method of claim 1, wherein the D90 of the particles of indomethacin, on a particle volume basis, is selected from the group consisting of:

less than 3000 nm, less than 2000 nm, less than 1900 nm, less than 1800 nm, and less than 1700 nm.

9. The method of any of claims 1-8 wherein the millable grinding compound is selected from lactose and mannitol and wherein the facilitating agent is sodium lauryl sulfate.

10. A method for producing a solid unit dosage pharmaceutical composition comprising indomethacin, comprising:

dry milling a composition comprising indomethacin, a millable grinding compound and a facilitating agent in a mill containing a plurality of milling bodies for a time period sufficient to produce a composition comprising particles of indomethacin having a median particle size, on a particle volume basis, between 3,000 nm and 25 nm; and

processing the composition comprising particles of indomethacin into a solid unit dosage pharmaceutical composition containing 40 mg of indomethacin, wherein the solid unit dosage pharmaceutical composition, 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 66%, by weight, is released by 75 minutes.

11. The method of claim 10, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 66%, by weight, is released by 60 minutes.

12. The method of claim 10, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 66%, by weight, is released by 45 minutes.

13. The method of claim 10, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 66%, by weight, is released by 30 minutes.

14. The method of claim 10, wherein the solid unit dosage pharmaceutical composition has a dissolution rate of indomethacin such that at least 66%, by weight, is released by 20 minutes.

15. The method of claim 10, wherein the particles of indomethacin have a median particle size, on a volume average basis, between 25 nm and 1000 nm.

16. The method of claim 10, wherein the particles of indomethacin have a median particle size, on a volume average basis, between 25 nm and 700 nm.

17. The method of claim 10, wherein the D90 of the particles of indomethacin, on a particle volume basis, is selected from the group consisting of:

less than 3000 nm, less than 2000 nm, less than 1900 nm, less than 1800 nm, and less than 1700 nm.

18. The method of any of claims 10-17 wherein the millable grinding compound is selected from lactose and mannitol and wherein the facilitating agent is sodium lauryl sulfate.