Combination therapy for copd

Abstract

Aerosol formulations comprising glycopyrronium bromide in combination with formoterol are useful for the prevention or treatment of chronic obstructive pulmonary disease. The formulation further comprises a HFA propellant, a co-solvent, and an amount of inorganic acid sufficient to stabilize both the glycopyrronium bromide and the formoterol components. Optionally the formulation may further comprise beclometasone dipropionate.

1 . A pharmaceutical composition, comprising:
 (a) glycopyrronium bromide; and   (b) formoterol or a salt thereof;   dissolved in an HFA propellant and a co-solvent, wherein said composition comprises an acid in an amount equivalent to 0.1 to 0.3 μg/μl of 1M HCl.   
     
     
         2 . A composition according to  claim 1 , wherein said composition comprises an acid in an amount equivalent to 0.15 to 0.28 μg/μl of 1M HCl. 
     
     
         3 . A pharmaceutical composition according to  claim 1 , wherein the co-solvent is ethanol. 
     
     
         4 . A pharmaceutical composition according to  claim 1 , further comprising one or more pharmaceutically active ingredients selected from the group consisting of beta-2 agonists, corticosteroids, antimuscarinic agents, and phosphodiesterase (IV) inhibitors. 
     
     
         5 . A pharmaceutical composition according to  claim 4 , which further comprises beclometasone dipropionate. 
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein the concentration of glycopyrronium bromide is in the range 0.005 to 0.14% (w/w). 
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein the concentration of formoterol or a salt thereof is in the range 0.005 to 0.07% w/w. 
     
     
         8 . A pharmaceutical composition according to  claim 1 , which has been substantially purged of oxygen. 
     
     
         9 . An aerosol canister, comprising a pharmaceutical composition according to  claim 1 . 
     
     
         10 . A canister according to  claim 9 , from which oxygen has been substantially removed from the headspace. 
     
     
         11 . A method of filling a canister according to  claim 9 , comprising:
 (a) preparing a solution of glycopyrronium bromide, formoterol fumarate and optionally beclometasone dipropionate in a co-solvent to which an acid in an amount equivalent to 0.1 to 0.3 μg/μl of 1M HCl of the final solution has been added;   (b) filling an aerosol canister with said solution;   (c) placing a valve onto the can and (vacuum) crimping; and   (d) pressure-filling the canister with HFA propellant through the valve.   
     
     
         12 . A kit-of-parts, comprising a pharmaceutical composition according to  claim 1 , further comprising one or more pharmaceutically active ingredients for separate, sequential or simultaneous administration, wherein said pharmaceutically active ingredients are selected from the group consisting of beta agonists, corticosteroids, antimuscarinic agents, and phosphodiesterase (IV) inhibitors. 
     
     
         13 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 1  to a subject in need thereof. 
     
     
         14 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 2  to a subject in need thereof. 
     
     
         15 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 3  to a subject in need thereof. 
     
     
         16 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 4  to a subject in need thereof. 
     
     
         17 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 5  to a subject in need thereof. 
     
     
         18 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 6  to a subject in need thereof. 
     
     
         19 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 7  to a subject in need thereof. 
     
     
         20 . A method for the prevention or treatment of chronic obstructive pulmonary disease, comprising administering an effective amount of a pharmaceutical composition according to  claim 8  to a subject in need thereof.