Medicaments

Abstract

This invention relates to aerosol formulations of use for the administration of medicaments by inhalation. More particularly, the invention relates to a pharmaceutical aerosol formulation which comprises particulate salbutamol sulphate having a crystalline form in which the outer layer of the crystals is substantially non-amorphous; and 1,1,1,2-tetrafluoroethane. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of a pharmaceutical aerosol formulation as defined is also described.

1 . A process of forming a pharmaceutical aerosol formulation, said process comprising: 
 subjecting particulate salbutamol sulphate to a temperature of between about 0° C. and about 100° C. with a relative humidity of between about 20% to about 90% to form annealed particulate salbutamol sulphate; and    combining the annealed salbutamol sulphate with a propellant comprising 1,1,2-tetrafluoroethane to form a pharmaceutical aerosol formulation.    
     
     
         2 . The process according to  claim 1 , wherein said step of subjecting particulate salbutamol sulphate to a temperature of between about 0° C. and about 100° C. with a relative humidity of between about 20% to about 90% comprises subjecting particulate salbutamol sulphate to a temperature of between about 10° C. and about 50° C. with a relative humidity of between about 55% to about 65%.  
     
     
         3 . The process according to  claim 1 , wherein said step of subjecting particulate salbutamol sulphate to a temperature of between about 0° C. and about 100° C. with a relative humidity of between about 20% to about 90% comprises subjecting particulate salbutamol sulphate to a temperature of between about 20° C. and about 30° C. with a relative humidity of about 60%.  
     
     
         4 . The process according to  claim 1 , wherein the annealed particulate salbutamol sulphate is present in the pharmaceutical aerosol formulation in an amount from about 0.01 to about 1% w/w.  
     
     
         5 . The process according to  claim 1 , wherein the annealed particulate salbutamol sulphate is present in the pharmaceutical aerosol formulation an amount ranging from about 0.05 to about 0.2% w/w.  
     
     
         6 . The process according to  claim 1 , the pharmaceutical aerosol formulation consisting essentially of the annealed particulate salbutamol sulphate and 1,1,1,2-tetrafluoroethane as propellant.  
     
     
         7 . The process according to  claim 1 , wherein the annealed particulate salbutamol sulphate is substantially thermally inactive as measured by microcalorimetry at about 25° C. and between about 30% to about 90% relative humidity.  
     
     
         8 . The process according to  claim 7 , wherein the annealed particulate salbutamol sulphate is micronized and includes a recrystallized outer layer.  
     
     
         9 . The process according to  claim 7 , where the annealed particulate salbutamol sulphate has a water content of less than about 0.4% by weight.  
     
     
         10 . The process according to  claim 9 , wherein said annealed particulate salbutamol sulphate has a water content of less than about 0.35% by weight.  
     
     
         11 . A process of forming a pharmaceutical aerosol formulation, said process comprising: 
 subjecting particulate salbutamol sulphate to elevated temperatures under vacuum to form annealed particulate salbutamol sulphate; and    combining the annealed salbutamol sulphate with a propellant comprising 1,1,1,2-tetrafluoroethane to form a pharmaceutical aerosol formulation.    
     
     
         12 . The process according to  claim 11 , wherein said step of subjecting particulate salbutamol sulphate to elevated temperatures under vacuum to form annealed particulate salbutamol sulphate comprises subjecting particulate salbutamol sulphate to a temperature of from about 40° C. to about 100° C.  
     
     
         13 . The process according to  claim 11 , wherein said step of subjecting particulate salbutamol sulphate to elevated temperatures under vacuum to form annealed particulate salbutamol sulphate comprises subjecting particulate salbutamol sulphate to a temperature greater than about 60° C.  
     
     
         14 . The process according to  claim 11 , wherein the annealed particulate salbutamol sulphate is present in the pharmaceutical aerosol formulation in an amount from about 0.01 to about 1% w/w.  
     
     
         15 . The process according to  claim 11 , wherein the annealed particulate salbutamol sulphate is present in the pharmaceutical aerosol formulation an amount ranging from about 0.05 to about 0.2% w/w.  
     
     
         16 . The process according to  claim 11 , the pharmaceutical aerosol formulation consisting essentially of the annealed particulate salbutamol sulphate and 1, 1, 1, 2-tetrafluoroethane as propellant.  
     
     
         17 . The process according to  claim 11 , wherein the annealed particulate salbutamol sulphate is substantially thermally inactive as measured by microcalorimetry at about 25° C. and between about 30% to about 90% relative humidity.  
     
     
         18 . The process according to  claim 17 , wherein the annealed particulate salbutamol sulphate is micronized and includes a recrystallized outer layer.  
     
     
         19 . The process according to  claim 17 , where the annealed particulate salbutamol sulphate has a water content of less than about 0.4% by weight.  
     
     
         20 . The process according to  claim 20 , wherein said annealed particulate salbutamol sulphate has a water content of less than about 0.35% by weight.