Packaged, sealed container system for stable storage of an oxygen sensitive pharmaceutical formulation

Abstract

A packaged, sealed container system for stable storage of a formulation of an oxygen-sensitive pharmaceutical compound, the packaged, sealed container system comprising a primary container including therein a formulation of an oxygen-sensitive pharmaceutical compound, a secondary outer container comprising a first flexible sheet layer, an opposing second flexible sheet layer, and a seal disposed along a common peripheral edge of the first and second flexible sheet layers, such that the primary container is disposed between and enclosed by the first and second flexible sheet layers of the secondary outer container. An oxygen scavenger is also disposed between and enclosed by the first and second flexible sheet layers of the secondary outer container. The oxygen scavenger is in fluid communication with the contents of the primary container.

1 - 29 . (canceled) 
     
     
         30 . A packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation, the packaged, sealed container system comprising:
 a primary container comprising a ready-to-use, stable norepinephrine formulation therein, the ready-to-use, stable norepinephrine formulation comprising:
 0.01 mg/ml to less than 0.04 mg/ml norepinephrine; 
 sodium chloride; 
 a pH between 3.4 and 4.0; 
 a secondary container comprising a first flexible sheet layer, an opposing second flexible sheet layer, and a seal disposed along a common peripheral edge of the first and second flexible sheet layers, wherein the primary container is disposed between and enclosed by the first and second flexible sheet layers of the secondary container; and 
 an oxygen scavenger disposed between and enclosed by the first and second flexible sheet layers of the secondary container, the oxygen scavenger being in fluid communication with the contents of the primary container, 
 wherein the primary container is a plastic bag comprising a third flexible sheet layer, an opposing fourth flexible sheet layer, and a primary container seal disposed along a common peripheral edge of the third and fourth flexible sheet layers. 
   
     
     
         31 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the primary container has a single port, the single port comprising an administration port for delivering the ready-to-use, stable norepinephrine formulation to a patient. 
     
     
         32 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the third or the fourth flexible sheets are coextruded film laminates comprising a polypropylene layer. 
     
     
         33 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 32 , wherein the coextruded film laminates further comprise a polyamide layer. 
     
     
         34 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the first flexible sheet layer comprises a coextruded film including a metal foil. 
     
     
         35 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the opposing second flexible sheet layer comprises a transparent coextruded film configured to allow visual inspection into the secondary container. 
     
     
         36 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the opposing second flexible sheet layer is colored to protect the ready-to-use, stable norepinephrine formulation from light. 
     
     
         37 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the second flexible sheet layer has a water transmission rate less than 3.0 g/m 2 /day. 
     
     
         38 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the oxygen scavenger comprises iron powder, iron oxide powder, or a mixture thereof. 
     
     
         39 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the concentration of norepinephrine is between about 0.015 mg/ml and about 0.035 mg/ml. 
     
     
         40 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the concentration of norepinephrine is between about 0.015 mg/ml and about 0.020 mg/ml. 
     
     
         41 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the concentration of norepinephrine is between about 0.030 mg/ml and about 0.035 mg/ml. 
     
     
         42 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , comprising 0.9% sodium chloride. 
     
     
         43 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the pH is between about 3.5 and about 3.9. 
     
     
         44 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the ready-to-use, stable norepinephrine formulation has a dissolved oxygen level of less than 0.5 ppm after storage for at least 150 days at 25° C. 
     
     
         45 . The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 , wherein the ready-to-use, stable norepinephrine formulation has a dissolved oxygen level of less than 0.5 ppm after storage for at least 180 days at 25° C. 
     
     
         46 . A method of treating hypotension in a subject, the method comprising:
 opening the packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to  claim 30 ;   administering to a subject a therapeutically effective amount of the ready-to-use, stable norepinephrine formulation,   wherein the subject is in need of treatment for hypotension.   
     
     
         47 . The method of  claim 46 , wherein the subject has a condition selected from one or more of pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, myocardial infarction, septicemia, blood transfusion, and drug reactions. 
     
     
         48 . The method of  claim 46 , wherein the subject has a condition selected from one or more of cardiac arrest and profound hypotension.