Formulation comprising glycopyrrolate, method and apparatus

Abstract

A method is disclosed for making a pharmaceutical composition for pulmonary administration comprising co-jet milling glycopyrrolate and magnesium stearate, wherein the co-jet milled glycopyrrolate and magnesium stearate is then subjected to a conditioning step which includes exposure of the co-jet milled glycopyrrolate and magnesium stearate to humidity. A composition made by this method is also disclosed.

1 - 36 . (canceled) 
     
     
         37 . A particle formulation prepared by a process comprising:
 co-jet milling unmicronised glycopyrrolate and magnesium stearate with milling gas having a humidity below 20% Relative Humidity to produce micronized composite particles; and   subjecting the micronized composite particles to a conditioning step comprising exposing the micronized composite particles to humidity in the range of 10%-95% Relative Humidity at temperatures ranging from 5° C. to 88° C. for at least 60 minutes;   wherein the formulation further comprises indacaterol and mometasone.   
     
     
         38 . The particle formulation of  claim 37 , wherein the glycopyrrolate is a racemate. 
     
     
         39 . The particle formulation of  claim 37 , wherein the glycopyrrolate is a single enantiomer. 
     
     
         40 . The particle formulation of  claim 37 , wherein the magnesium stearate forms a coating on the surface of the glycopyrrolate particles as measured by energy-dispersive X-ray spectroscopy. 
     
     
         41 . The particle formulation of  claim 37 , wherein the span of the co-jet milled and co-conditioned glycopyrrolate and magnesium stearate agent is less than 150 prior to blending with carrier particles. 
     
     
         42 . The particle formulation of  claim 41 , wherein the span of the co-jet milled and co-conditioned glycopyrrolate and magnesium stearate agent is less than 50 prior to blending with carrier particles. 
     
     
         43 . The particle formulation of  claim 37 , wherein the fraction of the conditioned co-jet milled formulation which is greater than 10 μm is less than 20% by volume or mass immediately after the co-jet milling and after the conditioning process as suitably determined by laser diffraction equipment. 
     
     
         44 . The particle formulation of  claim 37 , wherein the micronized composite particles are blended with a carrier, optionally after the conditioning step. 
     
     
         45 . The particle formulation of  claim 44 , wherein the micronized composite particles are blended with alpha-lactose monohydrate, optionally after the conditioning step. 
     
     
         46 . A particle formulation prepared by a process comprising:
 co-jet milling unmicronised glycopyrrolate and magnesium stearate with milling gas having a humidity below 20% Relative Humidity to produce micronized composite particles;   subjecting the micronized composite particles to a conditioning step comprising exposing the micronized composite particles to humidity in the range of 10%-95% Relative Humidity at temperatures ranging from 5° C. to 88° C. for at least 10 minutes; and   subsequently adding indacaterol and mometasone to the formulation.   
     
     
         47 . The particle formulation of  claim 46 , wherein the glycopyrrolate is a racemate. 
     
     
         48 . The particle formulation of  claim 46 , wherein the glycopyrrolate is a single enantiomer. 
     
     
         49 . The particle formulation of  claim 46 , wherein the magnesium stearate forms a coating on the surface of the glycopyrrolate particles as measured by energy-dispersive X-ray spectroscopy. 
     
     
         50 . The particle formulation of  claim 46 , wherein the span of the co-jet milled and co-conditioned glycopyrrolate and magnesium stearate agent is less than 150 prior to blending with carrier particles. 
     
     
         51 . The particle formulation of  claim 46 , wherein the span of the co-jet milled and co-conditioned glycopyrrolate and magnesium stearate agent is less than 50 prior to blending with carrier particles. 
     
     
         52 . The particle formulation of  claim 46 , wherein the fraction of the conditioned co-jet milled formulation which is greater than 10 μm is less than 20% by volume or mass immediately after the co-jet milling and after the conditioning process as suitably determined by laser diffraction equipment. 
     
     
         53 . The particle formulation of  claim 46 , wherein the micronized composite particles are blended with a carrier, optionally after the conditioning step. 
     
     
         54 . The particle formulation of  claim 53 , wherein the micronized composite particles are blended with alpha-lactose monohydrate, optionally after the conditioning step. 
     
     
         55 . A particle formulation prepared by a process comprising:
 co-jet milling unmicronised glycopyrrolate and magnesium stearate with milling gas having a humidity below 20% Relative Humidity to produce micronized composite particles; and   subjecting the micronized composite particles to a conditioning step comprising exposing the micronized composite particles to humidity in the range of 10%-95% Relative Humidity at temperatures ranging from 5° C. to 88° C. for at least 10 minutes;   wherein the formulation further comprises indacaterol and mometasone.