Methods for determining chemical heterogeneity of glass containers

Abstract

A method of making a glass container for storing a pharmaceutical formulation includes heating a Type 1 glass composition according to ASTM Standard E438-92 (2011) to form a glass melt, and forming the glass melt into a glass tube. The glass tube is then re-formed into the glass container having a glass body with: a wall region with an interior surface and an exterior surface; a heel region; and a base region. The interior surface of the glass container is formed by the interior surface of the glass body. A glass pharmaceutical container has a CDR value of less than or equal to 6.0, at least a class A2 base resistance or better according to ISO 695, at least a type HGB2 hydrolytic resistance or better according to ISO 719, and Type 1 chemical durability according to USP <660>.

1 . A method of making a glass container for storing a pharmaceutical formulation, the method comprising:
 heating a Type 1 glass composition according to ASTM Standard E438-92 (2011) to form a glass melt;   forming the glass melt into a glass tube;   re-forming the glass tube into the glass container comprising a glass body having a wall region with an interior surface and an exterior surface, a heel region, and a base region, wherein the interior surface of the glass container is formed by the interior surface of the glass body, and wherein
 the glass container has a CDR value of less than or equal to 6.0, 
 the glass container has at least a class A2 base resistance or better according to ISO 695, 
 the glass container has at least a type HGB2 hydrolytic resistance or better according to ISO 719, and 
 the glass container has Type 1 chemical durability according to USP <660>. 
   
     
     
         2 . The method of  claim 1 , wherein the glass container has a CDR value that is greater than or equal to 0.6 and less than or equal to 1.6. 
     
     
         3 . The method of  claim 1 , wherein the glass container has a CDR value that is greater than or equal to 0.8 and less than or equal to 1.2. 
     
     
         4 . The method of  claim 1 , wherein the glass container has a type HGB1 hydrolytic resistance according to ISO 719. 
     
     
         5 . The method of  claim 1 , wherein calculating the CDR value comprises the following steps:
 obtaining a plurality of glass containers;   adding to each glass container of the plurality of the glass containers a solvent such that a volume of the solvent in each glass container comprises from greater than or equal to 5.0% by volume of the glass container to less than or equal to 50.0% by volume of the glass container;   heating the plurality of glass containers to a temperature from 90° C. to 130° C.;   cooling the plurality of glass containers to room temperature;   removing and consolidating the solvent from the plurality of glass containers to obtain a consolidated solvent;   titrating the consolidated solvent, wherein an amount of a titrant used in titrating the consolidated solvent is an as received titrant volume;   etching each glass container of the plurality of glass containers by contacting at least the interior surface of the each glass container with an etchant, wherein the etching removes a layer of the interior surface of each glass container, the layer having a thickness from greater than or equal to 0.75 μm to less than or equal to 15 μm to obtain a plurality of etched glass containers;   rinsing each etched glass container of the plurality of etched glass containers to remove residual etchant;   adding to each etched glass container of the plurality of etched glass containers a second solvent such that a volume of the second solvent in each etched glass container comprises from greater than or equal to 5.0% by volume of the etched glass container to less than or equal to 50.0% by volume of the etched glass container;   heating the plurality of etched glass containers to temperatures from 90° C. to 130° C.;   cooling the plurality of etched glass containers to room temperature;   removing and consolidating the second solvent from the plurality of etched glass containers to obtain an etched consolidated solvent;   titrating the etched consolidated solvent, wherein an amount of a titrant used in titrating the etched consolidated solvent is an etched titrant volume;   calculating a Chemical Durability Ratio (CDR) of the plurality of glass containers where:   
       
         
           
             
               CDR 
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                     Received 
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                     Titrant 
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                     Volume 
                   
                   
                     Etched 
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                     Titrant 
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                     Volume 
                   
                 
                 . 
               
             
           
         
       
     
     
         6 . The method according to  claim 5 , wherein the solvent added to each glass container of the plurality of the glass containers comprises from greater than or equal to 8.0% by volume of the glass container to less than or equal to 25.0% by volume of the glass container, and
 the second solvent added to each etched glass container of the plurality of etched glass containers comprises from greater than or equal to 8.0% by volume of the glass container to less than or equal to 25.0% by volume of the etched glass container.   
     
     
         7 . The method according to  claim 5 , wherein the solvent added to each glass container of the plurality of the glass containers comprises about 12.5% by volume of the glass container, and
 the second solvent added to each etched glass container of the plurality of etched glass containers comprises about 12.5% by volume of the glass container.   
     
     
         8 . The method according to  claim 5 , wherein after the CDR is determined, the method further comprises:
 (a) etching a second plurality of glass containers by adding an etchant to each glass container of the second plurality of glass containers, wherein the etching removes a layer of an interior surface of each glass container of the second plurality of glass containers, the layer having a thickness from greater than or equal to 50 nm to less than or equal to 250 nm;   (b) rinsing each glass container of the second plurality of glass containers to remove residual etchant;   (c) adding to each glass container of the second plurality of glass containers a third solvent such that a volume of the third solvent in each glass container of the second plurality of glass containers comprises from greater than or equal to 8.0% by volume of a glass container of the second plurality of glass containers to less than or equal to 25.0% by volume of a glass container of the second plurality of the glass containers;   (d) heating the second plurality of glass containers to a temperature from 90° C. to 130° C.;   (e) cooling the second plurality of glass containers to room temperature;   (f) removing and consolidating the third solvent from the second plurality of etched glass containers to obtain a second etched consolidated solvent;   (g) titrating the second etched consolidated solvent, wherein an amount of a titrant used in titrating the second etched consolidated solvent is a titration volume of an interval;   (h) repeating (a)-(g) until a total thickness of the interior surface of the glass container removed by etching is from greater than or equal to 0.75 μm to less than or equal to 15 μm;   (i) calculating a second Chemical Durability Ratio (CDR) of the plurality of glass containers where:   
       
         
           
             
               CDR 
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                 . 
               
             
           
         
       
     
     
         9 . The method according to  claim 5 , wherein heating the plurality of glass containers comprises:
 placing the plurality of glass containers into an autoclave;   heating the autoclave to about 100° C.;   holding the autoclave at about 100° C. for about 10 minutes;   heating the autoclave from about 100° C. to about 121° C. at a rate of about 1° C. per minute;   holding the autoclave at about 121° C. for about 60 minutes; and   cooling the autoclave from about 121° C. to about 100° C. at a rate of about 0.5° C. per minute.   
     
     
         10 . The method according to  claim 5 , wherein the consolidated solvent and the etched consolidated solvent are titrated with 0.01 M HCl. 
     
     
         11 . A glass pharmaceutical container comprising:
 a glass body having a wall region with an interior surface and an exterior surface, a heel region, and a base region, wherein the interior surface of the glass container is formed by the interior surface of the glass body, and wherein
 the glass container has a CDR value of less than or equal to 6.0, 
 the glass container has at least a class A2 base resistance or better according to ISO 695, 
 the glass container has at least a type HGB2 hydrolytic resistance or better according to ISO 719, and 
 the glass container has Type 1 chemical durability according to USP <660>. 
   
     
     
         11 . The glass pharmaceutical container of  claim 10 , wherein the glass pharmaceutical container has a CDR value that is greater than or equal to 0.6 and less than or equal to 1.6. 
     
     
         12 . The glass pharmaceutical container of  claim 10 , wherein the glass pharmaceutical container has a CDR value that is greater than or equal to 0.8 and less than or equal to 1.2. 
     
     
         13 . The glass pharmaceutical container of  claim 10 , wherein the glass pharmaceutical container has a type HGB1 hydrolytic resistance according to ISO 719.