Pharmaceutical solution formulations for pressurised metered dose inhalers

Abstract

The invention relates to the prevention and/or treatment of a severe broncho-pulmonary disease by administering a solution formulation from a pressurized metered dose inhaler capable of providing therapeutical doses of two or more active drug substances to the lung, wherein all the active drug substances are fully dissolved in the formulation as well as the two or more active drug substances are delivered with substantially the same particle size distribution.

1 . A method for the prevention and/or treatment of a severe broncho-pulmonary disease, which comprises administering to a subject in need thereof an effective amount of a pressurized solution formulation from a metered dose inhaler, which comprises two or more active drug substances in a predetermined ratio dissolved in an HFA propellant and a co-solvent, wherein, on actuation of said inhaler, substantially all of the liquid particles emitted 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 and said two or more active drug substances are delivered with substantially the same particle size distribution. 
   
   
       2 . The method according to  claim 1 , wherein said formulation comprises at least one beta 2 -agonist. 
   
   
       3 . The method according to  claim 1 , wherein said formulation comprises at least one member selected from the group consisting of formoterol, carmoterol, indacaterol salmeterol, stereoisomers, a salt thereof, a solvate thereof, a solvate of a salt thereof, and mixtures thereof. 
   
   
       4 . The method according to  claim 1 , wherein said formulation comprises formoterol fumarate. 
   
   
       5 . The method according to  claim 1 , wherein said formulation comprises carmoterol hydrochloride. 
   
   
       6 . The method according to  claim 1 , wherein said formulation comprises an inhaled corticosteroid. 
   
   
       7 . The method according to  claim 1 , wherein said formulation comprises 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. 
   
   
       8 . The method according to  claim 1 , wherein said formulation comprises beclometasone dipropionate or budesonide. 
   
   
       9 . The method according to  claim 1 , wherein said formulation comprises an anticholinergic atropine-like derivative or an antimuscarinic M3 inhibitor. 
   
   
       10 . The method according to  claim 1 , wherein said formulation comprises at least one member selected from the group consisting of ipratropium bromide, oxitropium bromide, tiotropium bromide, glycopyrronium bromide, and mixtures thereof. 
   
   
       11 . The method according to  claim 1 , wherein said formulation comprises ethanol in an amount between 5% and 20% w/w, based on the total weight of said formulation. 
   
   
       12 . The method according to  claim 1 , wherein said broncho-pulmonary disease is severe persistent asthma. 
   
   
       13 . The method according to  claim 1 , wherein said broncho-pulmonary disease is severe or very severe chronic obstructive pulmonary disease (COPD). 
   
   
       14 . A method for improving the co-deposition of two or more active drug substances in the lung tract of a patient, comprising administering a pressurized solution formulation from a metered dose inhaler, which comprises two or more active drug substances in a predetermined ratio dissolved in an HFA propellant and not more than 20% w/w ethanol as a co-solvent, wherein, on actuation of said inhaler, substantially all of the liquid particles emitted 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 drugs and said two or more active drug substances are delivered with substantially the same particle size. 
   
   
       15 . The method according to  claim 14 , wherein said formulation comprises at least one beta 2 -agonist. 
   
   
       16 . The method according to  claim 14 , wherein said formulation comprises at least one member selected from the group consisting of formoterol, carmoterol, indacaterol salmeterol, stereoisomers, a salt thereof, a solvate thereof, a solvate of a salt thereof, and mixtures thereof. 
   
   
       17 . The method according to  claim 14 , wherein said formulation comprises formoterol fumarate. 
   
   
       18 . The method according to  claim 14 , wherein said formulation comprises carmoterol hydrochloride. 
   
   
       19 . The method according to  claim 14 , wherein said formulation comprises an inhaled corticosteroid. 
   
   
       20 . A metered dose inhaler, which contains a solution formulation which comprises two or more active drug substances in a predetermined ratio dissolved in an HFA propellant and ethanol as a co-solvent, wherein, on actuation of said inhaler, substantially all of the liquid particles emitted 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 and said two or more active drug substances are delivered with substantially the same particle size distribution.