Inhalation particles incorporating a combination of two or more active ingredients

Abstract

Crystalline spherical inhalation particles incorporating a combination of two or more different active ingredients and a process for the preparation thereof. The particles have a narrow particle size distribution, rough surfaces and improved stability. The inhalation particles of the invention are particularly useful in the administration of a combination medicament, e.g. a combination of an anti-inflammatory agent and a bronchodilator, by inhalation in the treatment of asthma and other respiratory disorders.

1 - 21 . (canceled) 
     
     
         22 . Inhalation particles incorporating, in an unagglomerated individual particle, a combination of two or more different active ingredients, wherein said particles are spherical and at least one of the active ingredients is in crystalline form. 
     
     
         23 . Inhalation particles according to  claim 22 , wherein the mean mass aerodynamic diameter of said particles is about 1-5 μm. 
     
     
         24 . Inhalation particles according to  claim 22 , wherein the aerodynamic particle size distribution of said particles is about 0.5-10 μm. 
     
     
         25 . Inhalation particles according to  claim 22 , wherein the ratio of the active ingredients is constant. 
     
     
         26 . Inhalation particles according to  claim 22 , wherein the particles have a rough surface. 
     
     
         27 . Inhalation particles according to  claim 22 , wherein the particles are uncharged. 
     
     
         28 . Inhalation particles according to  claim 22 , incorporating a combination of beclomethasone dipropionate and formoterol fumarate. 
     
     
         29 . An inhalation composition comprising particles incorporating, in an unagglomerated individual particle, a combination of two or more different active ingredients, wherein said particles are spherical and at least one of the active ingredients is in crystalline form. 
     
     
         30 . An inhalation composition according to  claim 29  additionally comprising one or more pharmaceutically acceptable additives, diluents or carriers. 
     
     
         31 . An inhalation composition according to  claim 29  in the form of dry inhalation powder. 
     
     
         32 . An inhalation composition according to  claim 29  in the form of pressurized metered dose inhalation suspension. 
     
     
         33 . An inhaler device comprising an inhalation composition according to  claim 29 . 
     
     
         34 . A method for preparing particles incorporating, in an unagglomerated individual particle, a combination of two or more different active ingredients comprising the steps of:
 providing liquid feed stock comprising two or more different active ingredients in a predetermined ratio:   atomising said liquid feed stock to create droplets:   suspending said droplets in a carrier gas;   passing said carrier gas and droplets suspended therein through a heated tube flow reactor under predetermined residence time and temperature history; and   collecting the particles produced.   
     
     
         35 . A method of  claim 34  wherein the liquid feed stock, comprising two or more different active ingredients in a predetermined ratio, is in the form of a solution. 
     
     
         36 . A method according to  claim 34 , wherein the carrier gas is selected from nitrogen gas or other inert gas. 
     
     
         37 . A method according to  claim 34 , wherein the particles are collected using a particle collection system selected from an electrostatic precipitator, a cyclone or a filter. 
     
     
         38 . A method according to  claim 37 , wherein the particle collection system is heated to a temperature above the boiling point temperature of the solution to prevent condensation. 
     
     
         39 . A method according to  claim 34 , wherein the liquid feedstock comprises beclomethasone dipropionate and formoterol fumarate as active ingredients. 
     
     
         40 . A method according to  claim 39 , wherein the liquid feed stock comprises ethanol as a solvent. 
     
     
         41 . Inhalation particles according to  claim 22 , wherein the aerodynamic particle size distribution of said particles is about 1-5 μm.