Ophthalmic solution of difluprednate

Patent metadata

Field	Value
Publication number	US-12383496-B2
Application number	US-202418430855-A
Country	US
Kind code	B2
Filing date	Feb 2, 2024
Priority date	Oct 16, 2015
Publication date	Aug 12, 2025
Grant date	Aug 12, 2025

Abstract

The present invention provides a method of treatment of inflammatory disorder of the eye, said method comprising administering into the eye of a person in need thereof, an aqueous solution comprising difluprednate as the sole active ingredient at a concentration of 0.02% to 0.04% weight by volume in an aqueous vehicle, wherein the solution is free of oil and wherein the solution is administered twice-a-day. The present invention also provides an ophthalmic solution comprising a. therapeutically effective concentration of difluprednate, a crystal growth inhibitor and pharmaceutically acceptable amounts of a solubilizer comprising a mixture of i. quaternary ammonium compound and ii. polyethoxylated castor oil, b. in an aqueous vehicle. wherein the crystal growth inhibitor is polyvinyl alcohol or its derivatives.

First claim

The invention claimed is:

1. A clear ophthalmic aqueous solution comprising:
(a) about 0.02% w/v to about 0.45% w/v difluprednate;
(b) about 0.1% w/v to about 5.0% w/v crystal growth inhibitor;
(c) about 0.002% w/v to about 0.08% w/v quaternary ammonium compound; and
(d) about 1.5% w/v to about 6.0% w/v polyethoxylated castor oil;
wherein osmolality of the solution is about 250 to about 375 mOsm/kg.

2. The clear ophthalmic aqueous solution of claim 1 , wherein the difluprednate is not in particulate form.

3. The clear ophthalmic aqueous solution of claim 1 , wherein the crystal growth inhibitor is polyvinyl alcohol or a derivative thereof.

4. The clear ophthalmic aqueous solution of claim 1 , wherein the quaternary ammonium compound is benzalkonium chloride.

5. The clear ophthalmic aqueous solution of claim 1 , wherein the osmolality of the solution is about 270 to about 350 mOsm/kg.

6. The clear ophthalmic aqueous solution of claim 1 , further comprising a preservative, a chelating agent, a pH adjusting agent, a cosolvent, a viscosity increasing agent, or a combination thereof.

7. The clear ophthalmic aqueous solution of claim 6 , wherein the preservative comprises biguanide, boric acid, N-lauroyl sarcosine, sodium salt of N-lauroyl sarcosine, or combination thereof.

8. The clear ophthalmic aqueous solution of claim 7 , comprising about 0.002% w/v to about 0.02% w/v polyhexamethylene biguanide, about 0.05% w/v to 1.5% w/v boric acid, about 0.01% w/v to 0.1% w/v N-lauroyl sarcosine, or combination thereof.

9. The clear ophthalmic aqueous solution of claim 6 , wherein the chelating agent comprises edetate disodium, ethylenediamine tetracetic acid, edetic acid, disodium edetate dihydrate, diethylenetriamine pentaacetic acid, or combination thereof.

10. The clear ophthalmic aqueous solution of claim 6 , comprising about 0.01% w/v to 0.1% w/v of the chelating agent.

11. The clear ophthalmic aqueous solution of claim 6 , wherein the pH adjusting agent comprises acetic acid, sodium acetate, tartaric acid, sodium tartrate, citric acid, sodium citrate, hydrochloric acid, sodium hydroxide, or combination thereof.

12. The clear ophthalmic aqueous solution of claim 6 , wherein the cosolvent comprises glycerol, propylene glycol, ethylene glycol, polyethylene glycol, glycofurol, or combination thereof.

13. The clear ophthalmic aqueous solution of claim 12 , comprising about 1.0% w/v to about 3.0% w/v glycerol.

14. The clear ophthalmic aqueous solution of claim 1 , wherein percent transmission of the solution is greater than 90% at 650 nm.

15. The clear ophthalmic aqueous solution of claim 1 , wherein pH of the solution is about 5.0 to about 6.0.

16. The clear ophthalmic aqueous solution of claim 1 , comprising (a) about 0.02% to about 0.04% w/v difluprednate, (b) about 0.5% w/v to about 3.0% w/v of the crystal growth inhibitor; (c) about 0.01% w/v to about 0.05% w/v of the quaternary ammonium compound; and (d) about 3.0% w/v to about 5.0% w/v of the polyethoxylated castor oil.

17. A method of treating an inflammatory disorder of the eye, comprising administering the clear ophthalmic aqueous solution of claim 6 into the eye of a person in need thereof.

18. The method of claim 17 , wherein the administering is twice daily.

19. The method of claim 17 , wherein the inflammatory disorder of the eye is pain and inflammation associated with ocular surgery and/or uveitis, wherein the uveitis is acute anterior uveitis, endogenous anterior uveitis, chronic uveitis, or a combination thereof.

20. The method of claim 17 , wherein the inflammatory disorder of the eye is acute anterior uveitis or chronic uveitis.

Assignees

• Sun Pharma Advanced Res Co Ltd

Inventors

• Khopade Ajay Jaysingh
• Halder Arindam
• Shah Ankit Shaileshkumar

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K47/186

  Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61P27/04

  Artificial tears; Irrigation solutions · CPC title