Epinephrine formulations

Abstract

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 - 20 . (canceled) 
     
     
         21 . A method for preparing an injectable, shelf-life stable, unit dose solution of epinephrine in a vial, comprising deoxygenating an aqueous solution comprising 0.5 to 1.5 mg/mL of epinephrine and/or salts thereof and a buffer system, by at least partially reducing the amount of oxygen in the headspace of the vial until the oxygen content is no more than about 15% v/v of the total gas in the headspace, optionally by adding an inert gas, to reduce the rate of formation and/or the concentration of oxidative degradants in the solution. 
     
     
         22 . The method of  claim 21 , wherein deoxygenating the solution comprises adding an inert gas selected from the group consisting of nitrogen and argon. 
     
     
         23 . The method of  claim 21 , wherein the oxygen content is no more than about 10% v/v. 
     
     
         24 . The method of  claim 21 , wherein the oxygen content is no more than about 5% v/v. 
     
     
         25 . The method of  claim 21 , further comprising adding an antioxidant to the solution. 
     
     
         26 . The method of  claim 21 , wherein shelf-life stability is determined by packaging the vial in a container closure system and measuring the oxidative degradants in the solution after storage at 25±2° C. and 60±5% relative humidity for at least 12 months. 
     
     
         27 . An injectable, shelf-life stable, unit dose solution of epinephrine in a vial prepared by the method of  claim 21 . 
     
     
         28 . The method of  claim 21 , wherein the oxidative degradants are selected from the group consisting of adrenochrome, adrenolutin, melanins, and analogs thereof. 
     
     
         29 . The method of  claim 21 , wherein the solution further comprises a transition metal complexing agent. 
     
     
         30 . The method of  claim 21 , wherein the solution further comprises a tonicity regulating agent. 
     
     
         31 . The method of  claim 21 , wherein the solution further comprises a preservative. 
     
     
         32 . The method of  claim 21 , wherein the aqueous solution consists of epinephrine, a buffer system consisting of a pH raising agent and a pH lowering agent, and a tonicity regulating agent. 
     
     
         33 . An injectable, shelf-life stable, unit dose solution of epinephrine in a vial prepared by the method of  claim 32 . 
     
     
         34 . The method of  claim 26 , wherein the concentration of oxidative degradants in the solution after 12 months is no more than about 1%. 
     
     
         35 . The method of  claim 21 , wherein the vial contains 1 mL of the solution.