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,
a tonicity regulating agent comprising sodium chloride,
a pH raising agent comprising tartaric acid and sodium hydroxide,
0.0457 mg/mL sodium metabisulfite,
a pH lowering agent comprising hydrochloric acid,
a transition metal complexing agent comprising EDTA, and
water,
wherein the composition comprises no more than about 1.5% total impurities after 2 months of storage in long term storage conditions.
2. The pre-filled syringe according to claim 1 , wherein the epinephrine and/or salts thereof is present at a concentration of 0.114 mg/m L.
3. The pre-filled syringe according to claim 1 , wherein the sodium chloride is present at a concentration of 9 mg/mL.
4. The pre-filled syringe according to claim 1 , wherein the tartaric acid is present at a concentration of 0.225 mg/mL.
5. The pre-filled syringe according to claim 1 , wherein the sodium hydroxide is present at a concentration of 0.1 mg/mL.
6. The pre-filled syringe according to claim 1 , wherein the hydrochloric acid is present at a concentration of 0.025 mg/mL.
7. The pre-filled syringe according to claim 1 , wherein the EDTA is present at a concentration of 0.02 mg/mL.
8. The pre-filled syringe according to claim 1 , wherein the composition comprises about 15% or less total impurities after 6 months of storage in accelerated storage conditions.
9. The pre-filled syringe according to claim 8 , wherein the total impurities comprise D-epinephrine.
10. The pre-filled syringe according to claim 1 , wherein the composition comprises about 10% or less total impurities after 3 months of storage in accelerated storage conditions.
11. The pre-filled syringe according to claim 10 , wherein the total impurities comprise D-epinephrine.
12. The pre-filled syringe according to claim 1 , wherein the total impurities comprise D-epinephrine.
13. The pre-filled syringe according to claim 1 , wherein the total impurities comprise D-epinephrine.
14. The pre-filled syringe according to claim 1 , wherein the composition comprises about 5% or less total impurities after 6 months of storage in long term storage conditions.
15. The pre-filled syringe according to claim 14 , wherein the total impurities comprise D-epinephrine.
16. A pre-filled syringe containing a composition, the composition consisting of:
epinephrine and/or salts thereof at a concentration of 0.114 mg/mL,
a tonicity regulating agent comprising sodium chloride at a concentration of 9 mg/mL,
a pH raising agent comprising tartaric acid at a concentration of 0.225 mg/mL and sodium hydroxide at a concentration of 0.1 mg/mL,
an antioxidant comprising sodium metabisulfite at a concentration of 0.0457 mg/mL,
a pH lowering agent comprising hydrochloric acid at a concentration of 0.025 mg/mL,
a transition metal complexing agent comprising EDTA at a concentration of 0.02 mg/mL, and
water,
wherein the composition comprises no more than about 1.5% total impurities after 2 months of storage in long term storage conditions.
17. The pre-filled syringe according to claim 1 , wherein the composition comprises no more than about 2.8% total impurities after 3 months of storage in long term storage conditions.
18. The pre-filled syringe according to claim 16 , wherein the composition comprises no more than about 2.8% total impurities after 3 months of storage in long term storage conditions.