EPINEPHRINE COMPOSITIONS AND CONTAINERS
A sterile storage stable ready-to-inject epinephrine composition contained within a flexible container and packaged within a secondary container, the composition including an aqueous pharmaceutically acceptable carrier containing epinephrine and a metal ion chelator, the epinephrine being present in a concentration of equal to or less than 0.07 mg/mL, substantially all of the epinephrine being an R-isomer, the composition having a pH of between 3.5-4.7, and the composition having, after storage of at least one month at 25° C., total impurities of equal or less than 0.7% and equal or less than 4% S-isomer content.
1 . A sterile, storage stable, ready-to-inject epinephrine composition comprising an aqueous pharmaceutically acceptable carrier containing epinephrine and a metal ion chelator,
wherein the epinephrine is present at a concentration of equal or less than 0.07 mg/ml,
wherein the metal ion chelator is present in the composition at a concentration of between about 1 and 50 μg/ml,
wherein substantially all of the epinephrine is an R-isomer,
wherein the composition has a pH of between 3.5-4.7, and
wherein the composition is prepared by a process comprising:
(a) preparing a solution of epinephrine and a metal ion chelator in an aqueous pharmaceutically acceptable carrier, wherein the solution has a pH of between 3.5-4.7;
(b) packaging the solution into a container under an inert gas; and
(c) autoclaving the solution to sterility, wherein sterilization increases S-isomer content to no more than 4%.
2 . The composition of claim 1 , wherein sterilization increases S-isomer content by no more than 1.5%.
3 . The composition of claim 1 , wherein sterilization increases S-isomer content by no more than 0.5%.
4 . The composition of claim 1 , wherein sterilization increases total impurities content by no more than 0.5%.
5 . The composition of claim 1 , wherein sterilization increases total impurities content by no more than 0.3%.
6 . The composition of claim 1 , wherein the composition has, after sterilization and storage of at least one month at 25° C., total impurities of equal or less than 0.7% and equal or less than 2% S-isomer content.
7 . The composition of claim 1 , wherein the composition has, after sterilization and storage of at least one month at 25° C., total impurities of equal or less than 0.5% and equal or less than 1% S-isomer content.
8 . The composition of claim 1 , further comprising a buffer at a concentration of between 1-25 mM.
9 . The composition of claim 1 , wherein the composition comprises dissolved oxygen in an amount of equal or less than 1.5 ppm O 2 .
10 . A sterile, storage stable, ready-to-inject epinephrine composition comprising an aqueous pharmaceutically acceptable carrier containing epinephrine and a metal ion chelator,
wherein the epinephrine is present at a concentration of equal or less than 0.07 mg/ml,
wherein the metal ion chelator is present in the composition at a concentration of between about 1 and 50 μg/ml,
wherein substantially all of the epinephrine is an R-isomer,
wherein the composition has a pH of between 3.5-4.7,
wherein the composition contains antioxidants in an amount of equal or less than about 0.01 wt %, and
wherein the composition is prepared by a process comprising:
(a) preparing a solution of epinephrine and a metal ion chelator in an aqueous pharmaceutically acceptable carrier having a pH of between 3.5-4.7;
(b) packaging the solution into a container under an inert gas; and
(c) autoclaving the solution to sterility, wherein sterilization increases S-isomer content to no more than 4%.
11 . The composition of claim 10 , wherein the epinephrine is present at a concentration of equal or less than 0.04 mg/ml.
12 . The composition of claim 11 , wherein the composition has, after storage of at least one month at 25° C., total impurities of equal or less than 0.5%.
13 . The composition of claim 10 , wherein the epinephrine is present at a concentration of equal or less than 0.02 mg/ml.
14 . The composition of claim 13 , wherein the composition has, after storage of at least one month at 25° C., total impurities of equal or less than 0.5%.
15 . The composition of claim 10 , wherein the composition is an autoclaved sterile composition, and wherein the S-isomer content after autoclaving and after storage of at least one month at 25° C. is equal or less than 1.3%.
16 . The composition of claim 10 , wherein the composition is an autoclaved sterile composition, and wherein the S-isomer content after autoclaving and after storage of at least one month at 25° C. is equal or less than 0.7%.
17 . The composition of claim 10 , wherein the composition comprises dissolved oxygen in an amount of equal or less than 1.5 ppm O 2 .
18 . The composition of claim 10 , wherein the composition further comprises a buffer at a concentration of between 1-25 mM.
19 . The composition of claim 10 , wherein the composition, after storage of at least one month at 25° C., changes pH no more than 0.1 pH units.
20 . The composition of claim 10 , wherein the composition comprises the metal ion chelator at a concentration of between about 1 and 50 μg/ml.