Claims for Patent: 12,539,283

Summary for Patent: 12,539,283

Title:	Epinephrine liquid formulations
Abstract:	The invention provides a stable, pharmaceutical formulation comprising epinephrine or a pharmaceutically acceptable salt thereof. The formulation includes an organic acid, a tonicity agent, and water, has a pH of about 3.0 to about 3.6, and is substantially free of a conjugate base of the organic acid.
Inventor(s):	Chaoju Xiao, Karen Liu
Assignee:	Fresenius Kabi USA LLC
Application Number:	US19/029,026
Patent Claims:	1. A pharmaceutical formulation comprising: epinephrine or a pharmaceutically acceptable salt thereof, citric acid; a tonicity agent; a sulfite antioxidant; and water; wherein the formulation has a pH of from 3.0 to 3.6 and is substantially free of a conjugate base of citric acid and an aminopolycarboxylic acid. 2. The formulation of claim 1, wherein the epinephrine or pharmaceutically acceptable salt thereof is present at a concentration of from 0.1 mg/mL to 10 mg/mL. 3. The formulation of claim 1, wherein the citric acid is present at a concentration of from 0.1 mg/mL to 25 mg/mL. 4. The formulation of claim 1, wherein a weight ratio of the epinephrine or pharmaceutically acceptable salt thereof to the citric acid is from 1:5 to 10:1. 5. The formulation of claim 1, wherein the sulfite antioxidant is sodium metabisulfite. 6. The formulation of claim 1, further comprising a preservative. 7. A pharmaceutical product comprising a container and the formulation of claim 1 contained therein. 8. The pharmaceutical product of claim 7, wherein the formulation has a pH drift of less than 0.3 pH units following storage of the product for at least 12 months at room temperature. 9. The pharmaceutical product of claim 7, wherein the formulation contains not more than 5% of total impurities and not more than 3% of S-epinephrine relative to the amount of epinephrine as determined by a peak area percent method by high-performance liquid chromatography after storage of the product for at least 12 months at room temperature. 10. A pharmaceutical formulation comprising: 0.5-2.0 mg/mL of epinephrine or a pharmaceutically acceptable salt thereof; 0.25-1.0 mg/mL of citric acid; a tonicity agent; a sulfite antioxidant; and water; wherein the formulation has a pH of from 3.0 to 3.6 and is substantially free of a conjugate base of citric acid and an aminopolycarboxylic acid. 11. The formulation of claim 10, wherein a weight ratio of the epinephrine or pharmaceutically acceptable salt thereof to the citric acid is from 1:1 to 4:1. 12. The formulation of claim 11, wherein the formulation has an osmolality of 260-320 mOsm/kg. 13. The formulation of claim 10, wherein the tonicity agent is sodium chloride. 14. The formulation of claim 10, wherein the sulfite antioxidant is sodium metabisulfite. 15. The formulation of claim 10, further comprising a paraben. 16. A pharmaceutical product comprising a container and the formulation of claim 10 contained therein. 17. The pharmaceutical product of claim 16, wherein the formulation has a pH drift of less than 0.3 pH units following storage of the product for at least 12 months at room temperature. 18. The pharmaceutical product of claim 16, wherein the formulation contains not more than 5% of total impurities and not more than 3% of S-epinephrine relative to the amount of epinephrine as determined by a peak area percent method by high-performance liquid chromatography after storage of the product for at least 12 months at room temperature. 19. A pharmaceutical formulation comprising: 1.0 mg/mL of epinephrine or a pharmaceutically acceptable salt thereof, 0.5 mg/mL of citric acid; 8.6 mg/mL of sodium chloride; 0.25 mg/mL of sodium metabisulfite; and water; wherein the formulation has a pH of from 3.0 to 3.6 and is substantially free of a conjugate base of citric acid and an aminopolycarboxylic acid. 20. The formulation of claim 19, further comprising 1 mg/mL of methylparaben. 21. A pharmaceutical product comprising a container and the formulation of claim 19 contained therein. 22. The pharmaceutical product of claim 21, wherein the formulation has a pH drift of less than 0.3 pH units following storage of the product for at least 12 months at room temperature. 23. The pharmaceutical product of claim 21, wherein the formulation contains not more than 5% of total impurities and not more than 3% of S-epinephrine relative to the amount of epinephrine as determined by a peak area percent method by high-performance liquid chromatography after storage of the product for at least 12 months at room temperature.