Pharmaceutical metered dose inhaler and methods relating thereto
Methods of preparing elastomeric gasket materials for use in metered dose inhalers that include contacting an elastomeric gasket material to be used in a metered dose inhaler, which gasket material comprises one or more extractable compounds, with a solution comprising an organic solvent under conditions sufficient to extract at least a portion of at least one of the one or more extractable compounds from the elastomeric gasket material are described. Sealing gaskets made by such methods as well as metering valves, metered dose inhalers, and drug products that include such gaskets are also described.
1. A method of manufacturing a metered dose inhaler (MDI), said method comprising:
contacting an elastomeric gasket material comprising acrylonitrile butadiene rubber and one or more extractable compounds including oleic acid, with a solution comprising a lower alcohol, wherein the solution is at a temperature of at least 40° C. to extract oleic acid from the elastomeric gasket material such that the gasket material comprises between about 0.04 and 0.17% oleic acid to form a MDI sealing gasket;
agitating the elastomeric gasket material and the solution, wherein the agitating of the elastomeric gasket material is performed subsequent to the contacting of the elastomeric gasket material with the solution;
providing other MDI components and a pharmaceutical aerosol formulation comprising salmeterol xianfoate and fluticasone propionate; and
assembling the MDI.
2. The method of claim 1 , wherein at least one of the one or more extractable compounds comprises at least one additional compound selected from the group consisting of nonylphenol isomers, 2,2′-methylenebis(6-tertbutyl-4-methylphenol), 2,2,4,6,6-pentamethylhept-3-ene, 3′-oxybispropanitrile, palmitic acid, and stearic acid.
3. The method of claim 1 , wherein the lower alcohol is ethanol or isopropanol.
4. The method of claim 1 , wherein the solution consists essentially of ethanol.
5. The method of claim 1 , wherein the elastomeric gasket material is contacted with the solution for 15 minutes or greater.
6. The method of claim 1 , wherein the elastomeric gasket material is contacted with the solution at a temperature of at least 60° C.
7. The method of claim 1 , wherein the elastomeric gasket material is contacted with the solution under reflux conditions for the solution.
8. The method of claim 1 , wherein the elastomeric gasket material is contacted with the solution under conditions sufficient to extract at least 20 percent of at least one of the one or more extractable compounds.
9. The method of claim 1 , wherein the elastomeric gasket material is contacted with the solution under conditions sufficient to extract at least 40 percent of at least one of the one or more extractable compounds.
10. A method of manufacturing a metered dose inhaler (MDI), said method comprising:
contacting an elastomeric gasket material comprising acrylonitrile butadiene rubber and one or more extractable compounds including oleic acid, with a solution comprising a lower alcohol, wherein the solution is at a temperature of at least 40° C. to extract oleic acid from the elastomeric gasket material such that the gasket material comprises between about 0.04 and 0.17% oleic acid to form a MDI sealing gasket;
agitating the elastomeric gasket material and the solution;
providing other MDI components and a pharmaceutical aerosol formulation comprising salmeterol xianfoate and fluticasone propionate; and
assembling the MDI;
wherein the contacting of the elastomeric gasket material with the solution occurs subsequent to the agitating of the elastomeric gasket material.
11. The method of claim 10 , wherein at least one of the one or more extractable compounds comprises at least one additional compound selected from the group consisting of nonylphenol isomers, 2,2′-methylenebis(6-tertbutyl-4-methylphenol), 2,2,4,6,6-pentamethylhept-3-ene, 3′-oxybispropanitrile, palmitic acid, and stearic acid.
12. The method of claim 10 , wherein the lower alcohol is ethanol or isopropanol.
13. The method of claim 10 , wherein the solution consists essentially of ethanol.
14. The method of claim 10 , wherein the elastomeric gasket material is contacted with the solution for 15 minutes or greater.
15. The method of claim 10 , wherein the elastomeric gasket material is contacted with the solution at a temperature of at least 60° C.
16. The method of claim 10 , wherein the elastomeric gasket material is contacted with the solution under reflux conditions for the solution.
17. The method of claim 10 , wherein the elastomeric gasket material is contacted with the solution under conditions sufficient to extract at least 20 percent of at least one of the one or more extractable compounds.
18. The method of claim 10 , wherein the elastomeric gasket material is contacted with the solution under conditions sufficient to extract at least 40 percent of at least one of the one or more extractable compounds.
19. A method of manufacturing a metered dose inhaler (MDI), said method comprising:
contacting an elastomeric gasket material comprising acrylonitrile butadiene rubber and one or more extractable compounds including oleic acid, with a solution comprising a lower alcohol, wherein the solution is at a temperature of at least 40° C. to extract oleic acid from the elastomeric gasket material such that the gasket material comprises between about 0.04 and 0.17% oleic acid to form a MDI sealing gasket;
agitating the elastomeric gasket material and the solution;
drying the elastomeric gasket material, wherein said drying step comprises exposing the elastomeric gasket material to a vacuum, providing other MDI components and a pharmaceutical aerosol formulation comprising salmeterol xianfoate and fluticasone propionate; and
assembling the MDI.
20. The method of claim 19 , wherein at least one of the one or more extractable compounds comprises at least one additional compound selected from the group consisting of nonylphenol isomers, 2,2′-methylenebis(6-tertbutyl-4-methylphenol), 2,2,4,6,6-pentamethylhept-3-ene, 3′-oxybispropanitrile, palmitic acid, and stearic acid.
21. The method of claim 19 , wherein the lower alcohol is ethanol or isopropanol.
22. The method of claim 19 , wherein the solution consists essentially of ethanol.
23. The method of claim 19 , wherein the elastomeric gasket material is contacted with the solution for 15 minutes or greater.
24. The method of claim 19 , wherein the elastomeric gasket material is contacted with the solution at a temperature of at least 60° C.
25. The method of claim 19 , wherein the elastomeric gasket material is contacted with the solution under reflux conditions for the solution.
26. The method of claim 19 , wherein the elastomeric gasket material is contacted with the solution under conditions sufficient to extract at least 20 percent of at least one of the one or more extractable compounds.
27. The method of claim 19 , wherein the elastomeric gasket material is contacted with the solution under conditions sufficient to extract at least 40 percent of at least one of the one or more extractable compounds.
28. A method of manufacturing a metered dose inhaler (MDI), said method comprising:
contacting an elastomeric gasket material comprising acrylonitrile butadiene rubber and one or more extractable compounds including oleic acid, with a solution consists of a lower alcohol, wherein the solution is at a temperature of at least 40° C. to extract oleic acid from the elastomeric gasket material such that the gasket material comprises between about 0.04 and 0.17% oleic acid to form a MDI sealing gasket;
agitating the elastomeric gasket material and the solution;
drying the elastomeric gasket material, wherein said drying step comprises exposing the elastomeric gasket material to a vacuum, providing other MDI components and a pharmaceutical aerosol formulation comprising salmeterol xianfoate and fluticasone propionate; and
assembling the MDI.