Ophthalmic solution of difluprednate

Patent metadata

Field	Value
Publication number	US-11000475-B2
Application number	US-201615768285-A
Country	US
Kind code	B2
Filing date	Oct 15, 2016
Priority date	Oct 16, 2015
Publication date	May 11, 2021
Grant date	May 11, 2021

Abstract

The present invention 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. Also, 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.

First claim

The invention claimed is:

1. A clear ophthalmic aqueous solution comprising:
a. about 0.02% w/v to about 0.04% w/v difluprednate,
b. about 0.5% w/v to about 3.0% w/v of a crystal growth inhibitor, and
c. a solubilizer comprising a mixture of:
i. about 0.01% w/v to about 0.05% w/v quaternary ammonium compound and
ii. about 1.5% w/v to about 6.0% w/v polyethoxylated castor oil,

in an aqueous vehicle;
wherein the crystal growth inhibitor is polyvinyl alcohol or derivative thereof, wherein the difluprednate is not in microparticulate form.

2. The clear ophthalmic aqueous solution according to claim 1 , wherein the therapeutically effective concentration of difluprednate is about 0.03% w/v to 0.04% w/v.

3. The clear ophthalmic aqueous solution according to claim 1 , wherein the quaternary ammonium compound is benzalkonium chloride.

4. The clear ophthalmic aqueous solution according to claim 1 , wherein the polyethoxylated castor oil is about 3.0% w/v to about 5.0% w/v.

5. The clear ophthalmic aqueous solution according to claim 4 , wherein the polyethoxylated castor oil is polyoxyl 35 castor oil.

6. The clear ophthalmic aqueous solution according to claim 1 , wherein the polyvinyl alcohol or derivative thereof is about 1.4% w/v.

7. The clear ophthalmic aqueous solution according to claim 1 , wherein the solution further comprises a preservative selected from the group consisting of biguanide, boric acid, n-lauryl sarcosine and mixtures thereof.

8. The clear ophthalmic aqueous solution according to claim 2 , wherein the solution is administered into the eye of a person in need thereof twice a day.

9. The clear ophthalmic aqueous solution according to claim 1 , wherein the solution percent transmission of the solution is more than 90%.

10. The clear ophthalmic aqueous solution according to claim 2 , wherein the difluprednate is 0.04% w/v.

11. The clear ophthalmic aqueous solution according to claim 1 , wherein the difluprednate is 0.03% w/v.

12. The clear ophthalmic aqueous solution according to claim 1 , wherein the polyvinyl alcohol or derivative thereof is about 3.0% w/v.

13. The clear ophthalmic aqueous solution according to claim 1 , wherein the quaternary ammonium compound is about 0.025% w/v.

14. The clear ophthalmic aqueous solution according to claim 1 , wherein the polyethoxylated castor oil is about 5.0% w/v.

15. A clear ophthalmic aqueous solution comprising:
a. about 0.03% w/v to about 0.04% w/v difluprednate,
b. about 0.5% w/v to about 3.0% w/v polyvinyl alcohol or derivative thereof,
c. about 0.01% w/v to about 0.05% w/v benzalkonium chloride; and
d. about 1.5% w/v to about 6.0% w/v polyoxyl 35 castor oil.

Assignees

• Sun Pharma Advanced Res Co Ltd

Inventors

• Khopade Ajay Jaysingh
• Halder Arindam
• Shah Ankit Shaileshkumar

Classifications

• A61K31/573 Primary

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61K47/02

  Inorganic compounds · 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

• A61K9/08 Primary

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K47/44

  Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) · CPC title