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 pre-filled syringe containing a composition, the composition comprising:
epinephrine and/or salts thereof,
an antioxidant present at a concentration of in the range of about 0.1 to 0.9 mg/mL,
a buffer system, the buffer system comprising tartaric acid,
sodium chloride as a tonicity regulating agent at a concentration of in the range of about 6 to 7.5 mg/mL,
a preservative, and
disodium edetate dihydrate as a transition metal complexing agent at a concentration of in the range of about 0.01 to 0.4 mg/mL,
wherein the buffer system provides a resistance to a pH change such that the composition has a pH of in the range of about 3.5 and 4.0 after 18 months of shelf life, and wherein after 18 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH, the composition comprises about 3% or less of D-Epinephrine.
2. The pre-filled syringe of claim 1 , wherein the composition has a pH of in the range of about 3.5 and 4.0 after 24 months of shelf life.
3. The pre-filled syringe of claim 1 , wherein the composition has a pH of in the range of about 3.5 and 4.0 after 30 months of shelf life.
4. The pre-filled syringe of claim 1 , wherein the composition has a pH of in the range of about 3.5 and 4.0 after 36 months of shelf life.
5. The pre-filled syringe of claim 1 , wherein the composition has an initial pH of in the range of about 3.5 and 4.5.
6. The pre-filled syringe of claim 1 , wherein the composition has a pH after 18 months of shelf life of no more than about 1 unit different than an initial pH of the composition.
7. The pre-filled syringe of claim 1 , wherein the composition has a pH after 24 months of shelf life of no more than about 1 unit different than an initial pH of the composition.
8. The pre-filled syringe of claim 1 , wherein the composition has a pH after 30 months of shelf life of no more than about 1 unit different than an initial pH of the composition.
9. The pre-filled syringe of claim 1 , wherein the composition has a pH after 36 months of shelf life of no more than about 1 unit different than an initial pH of the composition.
10. The pre-filled syringe of claim 1 , wherein the buffer system has a pKa value in the range of about 2 to 5.
11. The pre-filled syringe of claim 1 , wherein the buffer system has a pKa value in the range of about 3 to 4.5.
12. The pre-filled syringe of claim 1 , wherein the buffer system has a pKa value of about 4.
13. The pre-filled syringe of claim 1 , wherein the buffer system has a pKa value that is within 1 unit of an initial pH of the composition without the buffer system.
14. The pre-filled syringe of claim 1 , wherein the composition has an initial pH of about 4.
15. The pre-filled syringe of claim 1 , wherein after 24 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH, the composition comprises about 3% or less of D-Epinephrine.
16. The pre-filled syringe of claim 1 , wherein after 30 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH, the composition comprises about 3% or less of D-Epinephrine.
17. The pre-filled syringe of claim 1 , wherein after 36 months of storage at between 23° C. and 32° C. and between 55% RH and 70% RH, the composition comprises about 3% or less of D-Epinephrine.
18. The pre-filled syringe of claim 1 , wherein the composition with the buffer system has a higher pH after 18 months of shelf life than what it would otherwise have been without the presence of the buffer system.