CARBOXYLVINYL POLYMER-CONTAINING NANOPARTICLE SUSPENSIONS

• US 20150072011A1
• Filed: 11/12/2014
• Published: 03/12/2015
• Est. Priority Date: 12/03/2009
• Status: Active Grant

• Current Assignee: Harrow IP, LLC (Harrow, Inc.)
• Original Assignee: Alcon Research Limited (Nestle SA)
• Inventors: CHOWHAN, Masood A., GHOSH, Malay, ASGHARIAN, Bahram, HAN, Wesley Weshin
• Granted Patent: US 9,662,398 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• 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 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• 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 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention generally relates to suspension compositions having a carboxyvinyl polymer such as a carbomer, a galactomannan such as guar, and a borate compound. A sparingly soluble particulate compound such as nepafenac is also included in the compositions. The sparingly soluble particulate compound has a small particle size to enhance bioavailability of the compound.

Claims

1. A topically administrable aqueous ophthalmic suspension composition comprising:

a carboxyvinyl polymer at a concentration of 0.1 to 0.5 w/v %;

a galactomannan at a concentration of 0.1 to 0.4 w/v %;

borate at a concentration of 0.4 to 2.0 w/v %; and

a sparingly soluble particulate compound, said compound having a solubility in water at 25°

C. of 0.001 to 0.1 w/v % and a particle size of 50 to 700 nm.

2. A composition according to claim 1, further comprising a pH-adjusting agent in an amount sufficient to cause the composition to have a pH of 5.0 to 7.2.

3. A composition according to claim 1, further comprising a tonicity-adjusting agent in an amount sufficient to cause the composition to have an osmolality of 250 to 350 mOsm/kg.

4. A composition according to claim 1 wherein said sparingly soluble particulate compound is nepafenac at a concentration of 0.1 to 1.0 w/v %.

5. A composition according to claim 1 wherein said carboxyvinyl polymer is carbomer at a concentration of 0.4 w/v %.

6. A composition according to claim 1 further comprising a milling agent at a concentration of 0.005 to 0.1 w/v %.

7. A composition according to claim 6 wherein said milling agent is a surfactant or polymer.

8. A composition according to claim 7 wherein said milling agent is sodium carboxylmethylcellulose.

9. A composition according to claim 1 further comprising a metal chloride salt tonicity-adjusting agent.

10. A composition according to claim 9 wherein said metal chloride salt is sodium chloride at a concentration of 0.4 w/v %.

11. A composition according to claim 1 further comprising a non-ionic hydroxyl compound as a tonicity-adjusting agent.

12. A composition according to claim 1 further comprising both a preservative and a chelating agent.

13. A composition according to claim 12 wherein the preservative is benzalkonium chloride at a concentration of 0.005 w/v % and the chelating agent is edetate disodium at a concentration of 0.01 w/v %.

14. A composition according to claim 1 wherein said carboxyvinyl polymer is carbomer, said galactomannan is guar, said borate is boric acid, and said sparingly soluble particulate compound is nepafenac at a concentration of 0.1 to 1.0 w/v %.

15. A composition according to claim 14 comprising 0.4 w/v % carbomer, 0.2 w/v % guar, 0.5 w/v % boric acid, and 0.3 w/v % nepafenac.

16. A composition according to claim 15 wherein said nepafenac has an average particle size of 400 nm.

17. A method of treating ophthalmic disorders in a patient comprising topically administering to the patient a composition according to claim 1.

18. A method according to claim 17 wherein said ophthalmic disorder is selected from the group consisting of:

ocular surface and retinal disorders, glaucoma, dry eye, ocular surface pain, uveitis, scleritis, episcleritis, keratitis, surgically-induced inflammation, endophthalmitis, iritis, atrophic macular degeneration, retinitis pigmentosa, iatrogenic retinopathy, retinal tears and holes, macular edema, cystoid macular edema, diabetic macular edema, diabetic retinopathy, sickle cell retinopathy, retinal vein and artery occlusion, optic neuropathy, exudative macular degeneration, neovascular glaucoma, corneal neovascularization, cyclitis, sickle cell retinopathy, and pterygium.

19. A topically administrable ophthalmic suspension composition consisting essentially of

a) 0.3 w/v % nepafenac having a particle size of 50 to 700 nm;

b) 0.4 w/v % carbomer;

c) 0.2 w/v % guar;

d) 0.5 w/v % boric acid;

e) 0.06 w/v % sodium carboxymethylcellulose;

f) 0.4 w/v % sodium chloride;

g) 0.5 w/v % propylene glycol;

h) a pH-adjusting agent in an amount sufficient to cause the composition to have a pH of 7.0;

i) 0.005% (w/v) benzalkonium chloride;

j) 0.01% edetate disodium; and

k) purified water.

20. A method for maintaining the viscosity of a topical ophthalmic composition comprising 0.1 to 0.5 w/v % carbomer when said composition is topically applied to the eye, the method comprising:

adding galactomannan sufficient to provide a concentration of 0.1 w/v % to 0.4 w/v % galactomannan in said composition, and borate sufficient to provide a concentration of 0.4 w/v % to 0.6 w/v % in said composition.

21. A method according to claim 20, wherein said composition has a pH of 5.0 to 7.2.

22. A method according to claim 20, wherein said composition further comprises a sparingly soluble particulate compound.

23. A method according to claim 22, wherein said sparingly soluble particulate compound is nepafenac at a concentration of 0.3 w/v %.