Pharmaceutical solution formulations for pressurised metered dose inhalers

Abstract

A method for delivering two or more active drug substances to the lungs by inhalation from a single pressurized metered dose inhaler product, said inhaler containing a HFA/cosolvent based solution formulation wherein all the active drug substances are fully dissolved in the formulation.

1 . A method of delivering a combination of two or more active drug substances to at least one lung region tract of a subject in need thereof, comprising: 
 administering said two or more active drug substances to said subject by actuation of a pressurized single metered dose inhaler,    wherein said pressurized single metered dose inhaler contains a medicament which exists as a solution,    wherein said medicament comprises two or more active drug substances in a predetermined ratio dissolved in an HFA propellant and one or more co-solvents,    wherein at least one of said active drug substances is a long acting β 2 -adrenergic agonist,    wherein on actuation said inhaler emits liquid particles,    wherein substantially all of said liquid particles emitted on actuation of said inhaler contain said two or more active drug substances in a ratio which is substantially the same as said predetermined ratio of said two or more active drug substances in said medicament, and    wherein each of said two or more active drug substances is delivered with substantially the same particle size distribution at the same lung region tract.    
   
   
       2 . A method according to  claim 1 , wherein said β 2 -adrenergic agonist is at least one member selected from the group consisting of formoterol, carmoterol, salmeterol, stereoisomers, a salt thereof, a solvate thereof, a solvate of a salt thereof, and mixtures thereof.  
   
   
       3 . A method according to  claim 2 , wherein said medicament comprises a corticosteroid.  
   
   
       4 . A method according to  claim 3 , wherein said corticosteroid is at least one member selected from the group consisting of beclomethasone dipropionate, fluticasone propionate, budesonide, the 22R-epimer of budesonide, rofleponide, ciclesonide, mometasone furoate, triamcinolone, an ester of triamcinolone, and mixtures thereof.  
   
   
       5 . A method according to  claim 4 , wherein said ester of triamcinolone is triamcinolone acetonide.  
   
   
       6 . A method according to  claim 2 , wherein said medicament comprises an anticholinergic atropine-like derivative or an antimuscarinic M3 inhibitor.  
   
   
       7 . A method according to  claim 6 , wherein said anticholinergic atropine-like derivative is at least one member selected from the group consisting of ipratropium bromide, oxitropium bromide, tiotropium bromide, glycopyrronium bromide, and mixtures thereof.  
   
   
       8 . A method according to  claim 1 , wherein said medicament comprises a phosphodiesterase 4 (PDE4) inhibitor.  
   
   
       9 . A method according to  claim 3 , wherein said β 2 -adrenergic agonist is formoterol fumarate and said corticosteroid is beclometasone dipropionate.  
   
   
       10 . A method according to  claim 3 , wherein said β 2 -adrenergic agonist is carmoterol hydrochloride and said corticosteroid is budesonide.  
   
   
       11 . A method according to  claim 1 , wherein the HFA propellant comprises at least one member selected from the group consisting of HFA 134a, HFA 227, and mixtures thereof.  
   
   
       12 . A method according to  claim 1 , wherein said co-solvent comprises an alcohol.  
   
   
       13 . A method according to  claim 1 , wherein said co-solvent comprises ethanol.  
   
   
       14 . A pressurized single metered dose inhaler, 
 wherein said pressurized single metered dose inhaler contains a medicament which exists as a solution,    wherein said medicament comprises two or more active drug substances in a predetermined ratio dissolved in an HFA propellant and one or more co-solvents,    wherein at least one of said active drug substances is a long acting β 2 -adrenergic agonist,    wherein on actuation said inhaler emits liquid particles,    wherein on actuation of said inhaler substantially all of said liquid particles emitted on actuation of said inhaler contain said two or more active drug substances in a ratio which is substantially the same as said predetermined ratio of said two or more active drug substances in said medicament, and    each of said two or more active drug substances is delivered with substantially the same particle size distribution at the same lung region tract.    
   
   
       15 . An inhaler according to  claim 14 , wherein said β 2 -adrenergic agonist is at least one member selected from the group consisting of formoterol, carmoterol, salmeterol, stereoisomers, a salt thereof, a solvate thereof, a solvate of a salt thereof, and mixtures thereof.  
   
   
       16 . An inhaler according to  claim 15 , wherein said medicament comprises a corticosteroid.  
   
   
       17 . An inhaler according to  claim 16 , wherein said corticosteroid is at least one member selected from the group consisting of beclomethasone dipropionate, fluticasone propionate, budesonide, the 22R-epimer of budesonide, rofleponide, ciclesonide, mometasone furoate, triamcinolone, an ester of triamcinolone, and mixtures thereof.  
   
   
       18 . An inhaler according to  claim 17 , wherein said ester of triamcinolone is triamcinolone acetonide.  
   
   
       19 . An inhaler according to  claim 15 , wherein said medicament comprises an anticholinergic atropine-like derivative or an antimuscarinic M3 inhibitor.  
   
   
       20 . An inhaler according to  claim 19 , wherein said anticholinergic atropine-like derivative is at least one member selected from the group consisting of ipratropium bromide, oxitropium bromide, tiotropium bromide, glycopyrronium bromide, and mixtures thereof.  
   
   
       21 . An inhaler according to  claim 14 , wherein said medicament comprises a phosphodiesterase 4 (PDE4) inhibitor.  
   
   
       22 . An inhaler according to  claim 16 , wherein said β 2 -adrenergic agonist is formoterol fumarate and said corticosteroid is beclometasone dipropionate.  
   
   
       23 . An inhaler according to  claim 16 , wherein said β 2 -adrenergic agonist is carmoterol hydrochloride and said corticosteroid is budesonide.  
   
   
       24 . An inhaler according to  claim 14 , wherein the HFA propellant comprises at least one member selected from the group consisting of HFA 134a, HFA 227, and mixtures thereof.  
   
   
       25 . An inhaler according to  claim 14 , wherein said co-solvent comprises an alcohol.  
   
   
       26 . An inhaler according to  claim 14 , wherein said co-solvent comprises ethanol.