Glass containers and sealing assemblies for maintaining seal integrity at low storage temperatures

Abstract

A sealed pharmaceutical container includes a shoulder, a neck extending from the shoulder, and a flange extending from the neck. The flange includes an inclined sealing surface defining an opening in the sealed pharmaceutical container. The sealed pharmaceutical container also includes a sealing assembly including a stopper extending over the sealing surface of the flange and a cap securing the stopper to the flange. The stopper has a glass transition temperature (Tg) that is greater than or equal to −70° C. and less than or equal to −45° C. The sealing assembly maintains a helium leakage rate of the sealed pharmaceutical container of less than or equal to 1.4×10−6 cm3/s as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −45° C.

1 - 29 . (canceled) 
     
     
         30 . A method of sealing a sealed pharmaceutical container, the method comprising the steps of:
 providing a sealed pharmaceutical container comprising a shoulder, a neck extending from the shoulder and a flange extending from the neck, the flange comprising:
 an underside surface extending from the neck; 
 an outer surface extending from the underside surface, the outer surface defining an outer diameter of the flange; and 
 a sealing surface extending between the outer surface to an inner surface of the sealed pharmaceutical container that defines an opening; 
   inserting a pharmaceutical composition into the sealed pharmaceutical container;   providing a sealing assembly comprising a stopper extending over the sealing surface of the flange and covering the opening;   crimping a metal-containing cap over the stopper and against flange to thereby compress the stopper against the sealing surface; and   cooling the sealed pharmaceutical container to a temperature of less than or equal to −45° C., wherein, after the cooling of the sealed pharmaceutical container, the compression is maintained on the sealing surface such that a helium leakage rate of the sealed pharmaceutical container is less than or equal to 1.4×10 −6  cm 3 /s at the temperature.   
     
     
         31 . The method of  claim 30 , wherein the sealing surface extends at an angle relative to a plane extending through an end of the opening such that a distance between the sealing surface and the plane increases with decreasing radial distance from the outer surface. 
     
     
         32 . The method of  claim 31 , wherein the angle is greater than 5 degrees. 
     
     
         33 . The method of  claim 31 , wherein the angles is less than or equal to 45 degrees. 
     
     
         34 . The method of  claim 30 , wherein the stopper has a glass transition temperature (T g ) that is greater than or equal to −70° C. and less than or equal to −45° C. 
     
     
         35 . The method of  claim 30 , wherein the sealing assembly maintains the helium leakage rate of the sealed pharmaceutical container of less than or equal to 1.4×10′ cm 3 /s as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −80° C. 
     
     
         36 . The method of  claim 30 , wherein the sealing assembly maintains the helium leakage rate of the sealed pharmaceutical container of less than or equal to 1.4×10′ cm 3 /s as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −100° C. 
     
     
         37 . The method of  claim 30 , wherein the sealing surface comprises a surface roughness of less than or equal to 0.1 μm. 
     
     
         38 . The method of  claim 37 , wherein the surface roughness of the sealing surface is predetermined based at least in part on an estimated shrinkage of a sealing assembly associated with the glass container when the sealing assembly is cooled to temperatures less than or equal to −80° C. 
     
     
         39 . The method of  claim 30 , wherein a surface flatness of the sealing surface is less than or equal to 5 μm. 
     
     
         40 . The method of  claim 30 , wherein the sealed pharmaceutical container is constructed of a glass composition having a coefficient of thermal expansion (CTE) that is greater than or equal to 0×10 −7 /K and less than or equal to 70×10 −7 /K. 
     
     
         41 . The method of  claim 30 , wherein the stopper comprises a radially heterogeneous composition. 
     
     
         42 . The method of  claim 30 , wherein the stopper has a coefficient of thermal expansion (CTE) of less than or equal to 290×10 −7 /K and a glass transition temperature (T g ) that is greater than or equal to −70° C. and less than or equal to −45° C. 
     
     
         43 . The method of  claim 30 , wherein the metal-containing cap has a CTE of greater than or equal to 260×10 −7 /K.