Stable preservative-free mydriatic and anti-inflammatory solutions for injection

Patent metadata

Field	Value
Publication number	US-9855246-B2
Application number	US-201615278514-A
Country	US
Kind code	B2
Filing date	Sep 28, 2016
Priority date	Oct 24, 2012
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

Abstract

The present invention relates to stable, preservative- and antioxidant-free liquid formulations of phenylephrine and ketorolac for injection.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A liquid intraocular ophthalmic pharmaceutical solution dosage form consisting essentially of phenylephrine, ketorolac, and a buffer system, in solution in a pH-adjusted aqueous carrier as a solvent, that is free of preservatives, antioxidants and solubilizing agents, and a nitrogen gas overlay in a single-use container, wherein the phenylephrine is included at a concentration of 45 mM to 76 mM and the ketorolac is included at a concentration of about 8.5 mM to 14 mM, wherein the intraocular ophthalmic pharmaceutical solution is stable for a period of at least six months when stored at a temperature of from 5+/−3° C. to 25+/−2° C.

2. The dosage form of claim 1 , wherein the dosage form is free of visible precipitation and crystallization.

3. The dosage form of claim 2 , wherein the intraocular ophthalmic pharmaceutical solution is stable for a period of at least 24 months when stored at a temperature of from 5+/−3° C. to 25+/−2° C.

4. The dosage form of claim 3 , wherein the intraocular ophthalmic pharmaceutical solution is stable for a period of at least 30 months when stored at a temperature of from 5+/−3° C. to 25+/−2° C.

5. The dosage form of claim 1 , wherein the buffer system comprises an about 20 mM sodium citrate buffer system.

6. The dosage form of claim 1 , wherein the phenylephrine is included at a concentration of about 60.75 mM and the ketorolac is included at a concentration of about 11.25 mM.

7. The dosage form of claim 1 , wherein the solution has a pH of from 5.8 to 6.8.

8. The dosage form of claim 7 , wherein the pH of the solution is adjusted by adding sodium hydroxide and/or hydrochloric acid as may be required.

9. The dosage form of claim 1 , wherein: the dosage form is free of visible precipitation and crystallization; the buffer system comprises an about 20 mM sodium citrate buffer system; the phenylephrine is included at a concentration of about 60.75 mM and the ketorolac is included at a concentration of about 11.25 mM; the solution has a pH of from 5.8 to 6.8 that has been adjusted with sodium hydroxide and/or hydrochloric acid as may be required.

10. A liquid intraocular ophthalmic pharmaceutical solution consisting essentially of phenylephrine, ketorolac, and a sodium citrate buffer system, in solution in an aqueous carrier as a solvent that is adjusted to a pH of from 5.8 to 6.8, that is free of preservatives, antioxidants and solubilizing agents, wherein the phenylephrine is included at a concentration of about 60.75 mM and the ketorolac is included at a concentration of about 11.25 mM, wherein the intraocular ophthalmic pharmaceutical solution is stable for a period of at least six months when stored at a temperature of from 5+/−3° C. to 25+/−2° C.

11. The solution of claim 10 , wherein the solution is free of visible precipitation and crystallization.

12. The solution of claim 10 , wherein the solution is stable for a period of at least 30 months when stored at a temperature of from 5+/−3° C. to 25+/−2° C.

13. A liquid intraocular ophthalmic pharmaceutical solution comprising phenylephrine, ketorolac, and a sodium citrate buffer system, in solution in an aqueous carrier as a solvent that is adjusted to a pH of from 5.8 to 6.8, that is free of preservatives, antioxidants and solubilizing agents, wherein the phenylephrine is included at a concentration of about 60.75 mM and the ketorolac is included at a concentration of about 11.25 mM, wherein the intraocular ophthalmic pharmaceutical solution is stable for a period of at least six months when stored at a temperature of from 5+/−3° C. to 25+/−2° C.

14. The solution of claim 13 , wherein the solution is free of visible precipitation and crystallization.

15. The solution of claim 13 , wherein the solution is stable for a period of at least 30 months when stored at a temperature of from 5+/−3° C. to 25+/−2° C.

Assignees

• Omeros Corp

Inventors

• Demopulos Gregory A
• Shen Hui-Rong
• Tedford Clark E

Classifications

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P27/04

  Artificial tears; Irrigation solutions · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P27/08

  Mydriatics or cycloplegics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title