Formulation of diclofenac

• US 9,180,095 B2
• Filed: 02/13/2015
• Issued: 11/10/2015
• 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): Krass, Frederick
• Assistant Examiner(s): Cohen, Michael P
• Application Number:
  US14/621,919
• Publication Number:
  US 20150157573A1
• Time in Patent Office: 270 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0087 Galenical forms not covered by A61K9/02 - A61K9/7023
• 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 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50
• 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 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/1682 Processes
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61K 9/4858 Organic 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 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61P 11/06 : Antiasthmatics
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 : for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/14 : for baldness or alopecia
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• 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: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10T 428/2982 : Particulate matter [e.g., sphere, flake, etc.]

Abstract

The present invention relates to methods for producing particles of diclofenac using dry milling processes as well as compositions comprising diclofenac, medicaments produced using diclofenac in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of diclofenac administered by way of said medicaments.

Claims

1. A method for treating pain comprising administering a solid oral unit dose of a pharmaceutical composition containing 18 mg of diclofenac acid to a subject, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 5000 nm and greater than 25 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 0.05% sodium lauryl sulfate in citric acid solution buffered to pH 5.75, has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 75 minutes.

2. The method of claim 1, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 3000 nm and greater than 25 nm.

3. The method of claim 2, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 60 minutes.

4. The method of claim 2, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 45 minutes.

5. The method of claim 2, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 30 minutes.

6. The method of claim 1, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 2000 nm and greater than 25 nm.

7. The method of claim 1, wherein the diclofenac acid have a median particle size, on a volume average basis, of less than 1900 nm and greater than 25 nm.

8. The method of claim 1, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 1700 nm and greater than 25 nm.

9. The method of claim 1, wherein the diclofenac acid have a median particle size, on a volume average basis, of less than 1500 nm and greater than 25 nm.

10. The method of claim 1, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 60 minutes.

11. The method of claim 1, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 45 minutes.

12. The method of claim 1, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 30 minutes.

13. The method of claim 1, wherein the pain is chronic pain or acute pain.

14. The method of claim 1, wherein the unit dose is administered at least once daily.

15. The method of claim 1, wherein a single unit dose provides perceptible pain relief.

16. A method for treating pain comprising administering a solid oral unit dose of a pharmaceutical composition containing 35 mg of diclofenac acid to a subject, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 5000 nm and greater than 25 nm, 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 0.05% sodium lauryl sulfate in citric acid solution buffered to pH 5.75, has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 75 minutes.

17. The method of claim 16, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 3000 nm and greater than 25 nm.

18. The method of claim 17, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 60 minutes.

19. The method of claim 17, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 45 minutes.

20. The method of claim 17, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 30 minutes.

21. The method of claim 16, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 2000 nm and greater than 25 nm.

22. The method of claim 16, wherein the diclofenac acid have a median particle size, on a volume average basis, of less than 1900 nm and greater than 25 nm.

23. The method of claim 16, wherein the diclofenac acid has a median particle size, on a volume average basis, of less than 1700 nm and greater than 25 nm.

24. The method of claim 16, wherein the diclofenac acid have a median particle size, on a volume average basis, of less than 1500 nm and greater than 25 nm.

25. The method of claim 16, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 60 minutes.

26. The method of claim 16, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 45 minutes.

27. The method of claim 16, wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 30 minutes.

28. The method of claim 16, wherein the pain is chronic pain or acute pain.

29. The method of claim 16, wherein the unit dose is administered at least once daily.

30. The method of claim 16, wherein a single unit dose provides perceptible pain relief.