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