NOVEL FORMULATION OF DICLOFENAC

• US 20130209569A1
• Filed: 01/25/2013
• Published: 08/15/2013
• 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, Norret, Marck, Russell, Adrian, Bosch, H William, Meiser, Felix
• Granted Patent: US 8,679,544 B2
• Time in Patent Office: Days
• US Class Current: 424/499
• 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 unit dose of a pharmaceutical composition containing 18 mg of diclofenac acid and comprising lactose monohydrate and sodium lauryl sulfate wherein the particles of diclofenac acid have a median particle size on a volume average basis of less than 500 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 at least 91%, by weight, is released by 45 minutes.

2. The unit dose of a pharmaceutical composition of claim 1, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 91%, by weight, is released by 30 minutes.

3. The unit dose of a pharmaceutical composition of claim 1, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 91%, by weight, is released by 15 minutes.

4. The unit dose of a pharmaceutical composition of claim 1, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 94%, by weight, is released by 45 minutes.

5. The unit dose of a pharmaceutical composition of claim 1, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 94%, by weight, is released by 30 minutes.

11. The unit dose of claim 1 wherein the median particle size on a particle volume basis is at least 25 nm.

13. The unit dose of claim 1 wherein the unit dose is a hard gelatin capsule.

15. The unit dose of claim 1 wherein the unit dose further comprises:

a binder, a lubricant, and a disintegrant.

17. The unit dose of claim 15 wherein the unit dose comprises microcrystalline cellulose, croscarmellose sodium, and sodium stearyl fumarate.

19. The unit dose of claim 1 wherein the D(90), on a particle volume basis, is selected from:

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

21. The unit dose of claim 1 wherein the T_max is selected from:

less than 5 hours, less than 4.5 hours, less than 4 hours, less than 3.5 hours, less than 3 hours, less than 3.5 hours, less than 2 hours, less than 1.75 hours, less than 1.5 hours, less than 1.25 hours, less than 1 hour, less than 40 minutes, and less than 30 minutes.

23. The unit dose of claim 1 wherein the time to first perceptible pain relief in a human patient administered a single dose is shorter than the time to first perceptible pain relief in a human patient administered 400 mg of celecoxib.

25. The unit dose of claim 1 wherein the time to peak pain relief in a human patient administered a single dose is shorter than the time to peak pain relief in a human patient administered 400 mg of celecoxib.

6. A unit dose of a pharmaceutical composition containing 35 mg of diclofenac acid and comprising lactose monohydrate and sodium lauryl sulfate wherein the particles of diclofenac acid have a median particle size on a volume average basis of less than 500 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 at least 82%, by weight, is released by 45 minutes.

7. The unit dose of a pharmaceutical composition of claim 6, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 82%, by weight, is released by 30 minutes.

8. The unit dose of a pharmaceutical composition of claim 6, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 82%, by weight, is released by 15 minutes.

9. The unit dose of a pharmaceutical composition of claim 6, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 95%, by weight, is released by 45 minutes.

10. The unit dose of a pharmaceutical composition of claim 6, wherein the unit dose has a dissolution rate of diclofenac acid such that at least 95%, by weight, is released by 30 minutes.

12. The unit dose of claim 6 wherein the median particle size on a particle volume basis is at least 25 nm.

14. The unit dose of claim 6 wherein the unit dose is a hard gelatin capsule.

16. The unit dose of claim 6 wherein the unit dose further comprises:

a binder, a lubricant, and a disintegrant.

18. The unit dose of claim 16 wherein the unit dose comprises microcrystalline cellulose, croscarmellose sodium, and sodium stearyl fumarate.

20. The unit dose of claim 6 wherein the D(90), on a particle volume basis, is selected from:

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

22. The unit dose of claim 6 wherein the Tmax is selected from:

less than 5 hours, less than 4.5 hours, less than 4 hours, less than 3.5 hours, less than 3 hours, less than 3.5 hours, less than 2 hours, less than 1.75 hours, less than 1.5 hours, less than 1.25 hours, less than 1 hour, less than 40 minutes, and less than 30 minutes.

24. The unit dose of claim 6 wherein the time to first perceptible pain relief in a human patient administered a single dose is shorter than the time to first perceptible pain relief in a human patient administered 400 mg of celecoxib.

26. The unit dose of claim 6 wherein the time to peak pain relief in a human patient administered a single dose is shorter than the time to peak pain relief in a human patient administered 400 mg of celecoxib.