Epinephrine formulations
Pharmaceutical compositions comprising epinephrine, methods of administration, and methods of making the same. Compositions may comprise at least one of an active agent, a pH raising agent, an antioxidant, a transition metal complexing agent, a pH lowering agent, a tonicity regulating agent, optionally a preservative, and optionally a solvent.
1. A composition comprising:
in the range of about 0.5 to 1.5 mg/mL of epinephrine and/or salts thereof,
in the range of about 6 to 8 mg/mL of a tonicity regulating agent,
in the range of about 2.8 to 3.8 mg/mL of a pH raising agent,
in the range of about 0.1 to 1.1 mg/mL of an antioxidant,
in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, and
in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent,
wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite.
2. The composition of claim 1 , wherein the tonicity regulating agent comprises sodium chloride.
3. The composition of claim 1 , wherein the pH raising agent comprises a buffer system comprising at least two compounds.
4. The composition of claim 1 , wherein the pH raising agent comprises at least one of tartaric acid and sodium hydroxide.
5. The composition of claim 1 , wherein the pH lowering agent comprises hydrochloric acid.
6. The composition of claim 1 , wherein the transition metal complexing agent comprises EDTA.
7. The composition of claim 1 , further comprising a preservative.
8. The composition of claim 7 , wherein the preservative comprises chlorobutanol.
9. The composition of claim 8 , wherein the preservative is present at a concentration of in the range of about 4.75 to 5.75 mg/mL.
10. The composition of claim 1 , further comprising a solvent.
11. The composition of claim 10 , wherein the solvent comprises water.
12. The composition according to claim 1 , wherein the composition comprises about 17% or less total impurities after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH,
wherein the impurities comprise epinephrine sulfonic acid (ESA), D-epinephrine, Impurity A, Impurity B, and Unknown C.
13. The composition according to claim 1 , wherein the composition comprises about 16% or less total impurities after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH,
wherein the impurities comprise epinephrine sulfonic acid (ESA), D-epinephrine, Impurity A, Impurity B, and Unknown C.
14. The composition of claim 1 , wherein the composition comprises about 11% or less of ESA after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH.
15. The composition of claim 1 , wherein the composition comprises about 3% or less of D-Epinephrine after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH.
16. The composition of claim 1 , wherein the composition comprises about 1% or less of Impurity A after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH.
17. The composition of claim 1 , wherein the composition comprises about 1% or less of Impurity B after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH.
18. The composition of claim 1 , wherein the composition comprises about 1% or less of Unknown C after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH.
19. The composition of claim 1 , wherein the composition does not undergo unacceptable color change after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH.