EPINEPHRINE FORMULATIONS FOR MEDICINAL PRODUCTS
The invention relates to compositions of epinephrine formulation in an aqueous solution that enhances the chemical stability of epinephrine and consequently extends the product shelf life. The formulation comprises epinephrine or a salt thereof, a tonicity modifier, and a complexing agent, in an aqueous solution adjusted to a pH of about 2-7. A process for manufacturing and methods of using the formulation for the medicinal products are also provided.
1 . An injectable pharmaceutical formulation comprising epinephrine or a salt thereof, a complexing agent, and a tonicity modifier in an aqueous solution, the injectable pharmaceutical formulation having an osmolality of about 200-400 mOsm/kg.
2 . The pharmaceutical formulation as in claim 1 , wherein the epinephrine or its salts as free base equivalent is in the range from 0.0001 wt. % to 5 wt. %.
3 . The pharmaceutical formulation as in claim 1 , wherein the epinephrine or its salts as free base equivalent is in the range 0.0001 wt. % to 1.0 wt. %.
4 . The pharmaceutical formulation as in claim 1 , wherein the epinephrine or its salts is selected from a group consisting of epinephrine, epinephrine bitartrate, and epinephrine hydrochloride.
5 . The pharmaceutical formulation as in claim 1 , wherein the complexing agent is cyclodextrin selected from a group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, modified α-cyclodexin, modified β-cyclodextin, modified γ-cyclodextrin, and combinations thereof.
6 . The pharmaceutical formulation as in claim 1 , wherein the complexing agent is sulfobutyl ether β-cyclodextrin.
7 . The pharmaceutical formulation as in claim 1 , wherein the complexing agent is hydroxyl propyl β-cyclodextrin.
8 . The pharmaceutical formulation as in claim 1 , wherein the molar ratio of cyclodextrin to epinephrine is in the range from 0.01:1 to 10:1.
9 . The pharmaceutical formulation as in claim 1 , further comprising a chelating agent.
10 . The pharmaceutical formulation as in claim 9 , wherein the chelating agent is edetic acid or a salt thereof.
11 . The pharmaceutical formulation as in claim 10 , wherein the chelating agent is edetate calcium disodium, edetate disodium, edetate disodium anhydrous, edetate sodium, or any combination thereof.
12 . The pharmaceutical formulation as in claim 1 , further comprising an antioxidant.
13 . The pharmaceutical formulation as in claim 12 , wherein the antioxidant is selected from the group consisting of oxine, boric acid, borate ascorbic acid, erythorbic acid, malic acid, acetylcysteine, thioglycerol, cysteine, citric acid, polyvinylpyrrolidone and combinations thereof.
14 . The pharmaceutical formulation as in claim 1 , wherein the aqueous solution has a pH of about 2-7.
15 . The pharmaceutical formulation as in claim 1 , further comprising a chelating agent.
16 . An injectable pharmaceutical formulation comprising epinephrine or a salt thereof, a complexing agent, and a tonicity modifier in an aqueous solution, the injectable pharmaceutical formulation having an osmolality of about 200-400 mOsm/kg, the epinephrine or a salt thereof being present in the composition in a free base equivalent amount of 0.0001 wt. % to 5 wt. %, the complexing agent being a cyclodextrin, and the molar ratio of cyclodextrin to epinephrine being in the range from 0.01:1 to 10:1.
17 . The pharmaceutical formulation as in claim 16 , wherein the epinephrine or its salts as free base equivalent is in the range 0.0001 wt. % to 1.0 wt. %.
18 . The pharmaceutical formulation as in claim 16 , wherein the complexing agent is sulfobutyl ether β-cyclodextrin, hydroxyl propyl β-cyclodextrin, or a combination thereof.
19 . A method for treating anaphylactic shock in a subject, said method comprising administrating to a subject in need thereof an effective amount of the formulation according to claim 16 .