Epinephrine compositions and containers
View Patent ↗The inventive subject matter provides ready-to-administer, preferably anti-oxidant free, epinephrine compositions with improved stability, and methods for preparing the same. Contemplated compositions can be packaged using blow-fill-seal technology or packaged into flexible IV bags and maintain degradation of the epinephrine at a level of less than 5 wt % when stored over at least one months at between 2-40° C.
1. An antioxidant-free and storage stable ready-to-inject epinephrine composition, comprising:
an aqueous pharmaceutically acceptable carrier containing epinephrine;
wherein the epinephrine is present in the ready-to-inject epinephrine composition at a concentration of equal or less than 0.07 mg/ml;
wherein substantially all of the epinephrine is an R-isomer;
wherein the ready-to-inject epinephrine composition has a pH of between 3.0-4.7;
wherein the ready-to-inject epinephrine composition further comprises a metal ion chelator present in the composition at a concentration of between about 1 and 50 ug/ml, wherein the metal ion chelator is selected from the group consisting of EDTA (edetic acid), EGTA, and diethylenetriaminepentaacetic acid; and
wherein the ready-to-inject epinephrine composition has, after storage of at least one month, total impurities of equal or less than 0.7% and equal or less than 2% S-isomer content.
2. The composition of claim 1 , wherein the epinephrine is present in the composition at a concentration of between about 0.005 mg/ml and 0.050 mg/ml.
3. The composition of claim 1 , wherein the epinephrine is present in the composition at a concentration of between about 0.006-0.010 mg/ml.
4. The composition of claim 1 , wherein the epinephrine is present in the composition at a concentration of between about 0.010-0.025 mg/ml.
5. The composition of claim 1 , wherein the epinephrine is present in the composition at a concentration of between about 0.025-0.045 mg/ml.
6. The composition of claim 1 , wherein the epinephrine is present in the composition as a pharmaceutically acceptable salt.
7. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after storage of at least one month, a pH of between about 3.5-4.5.
8. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after storage of at least one month, a pH of between about 3.8-4.2.
9. The composition of claim 1 , wherein the aqueous pharmaceutically acceptable carrier is water for injection.
10. The composition of claim 1 , wherein the aqueous pharmaceutically acceptable carrier further comprises a buffer.
11. The composition of claim 10 , wherein the buffer is present in a concentration of between 1 mM and 25 mM, and wherein the buffer is selected from the group consisting of an acetate buffer, a citrate buffer, a phosphate buffer, a tartrate buffer, and a borate buffer.
12. The composition of claim 1 , further comprising a tonicity agent selected from the group consisting of sodium chloride, glycerol, thioglycerol, mannitol, lactose, and dextrose.
13. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has dissolved oxygen of equal or less than 1.5 ppm O 2 .
14. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after storage of at least one month, total impurities of equal or less than 0.5% and equal or less than 1% S-isomer content.
15. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after storage of at least one month, total impurities of equal or less than 0.2% and equal or less than 1.5% S-isomer content.
16. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after storage of at least one month, total impurities of equal or less than 0.5% and equal or less than 1% S-isomer content.
17. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after storage of at least one month, total impurities of equal or less than 0.3% and equal or less than 0.7% S-isomer content.
18. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after autoclaving, total impurities of equal or less than 0.5% and equal or less than 2.0% S-isomer content.
19. The composition of claim 1 , wherein the ready-to-inject epinephrine composition has, after autoclaving, total impurities of equal or less than 0.2% and equal or less than 1.5% S-isomer content.
20. A pharmaceutical product, comprising:
a polymeric container comprising the antioxidant-free and storage stable ready-to-inject epinephrine composition of claim 1 , wherein the container is a blow-fill-seal (BFS) container or flexible IV bag;
wherein the polymeric container has a volume of between 100 mL and 1,000 mL; and
wherein the polymeric container is optionally enclosed in a metallized over-container that optionally further comprises an oxygen scavenger or absorber disposed between the polymeric container and the metallized over-container.