Powdery pharmaceutical compositions for inhalation

Abstract

Powdery pharmaceutical compositions including an active ingredient and carrier particles containing only a small amount of lubricant, 0.05-0.5% by weight, are used to prepare dry powder inhalers in order to increase the fine particle dose. A process for coating the surface of the carrier particles with such little amount of lubricant is also provided. Use of limited amount of lubricant is safe and provides ordered stable mixtures without segregation of the active particles during handling and before use.

What is claimed is:  
     
         1 . A powder for use in a dry powder inhaler, the powder including an active ingredient and a carrier, wherein the carrier further includes a lubricant in an amount up to 0.5% by weight of the total weight composition.  
     
     
         2 . A powder according to  claim 1  wherein the lubricant is present in an amount between about 0.1 and 0.5% by weight of the total weight of the composition.  
     
     
         3 . A powder according to  claim 1  or  2  wherein the lubricant particles at least partially coat the carrier particles surface.  
     
     
         4 . A powder according to  claim 1  wherein the lubricant is selected from magnesium stearate, stearic acid, sodium lauryl sulphate, sodium stearyl fumarate, stearyl alcohol, sucrose monopalmitate and sodium benzoate.  
     
     
         5 . A powder according to  claim 3  wherein the carrier particles are coated with 0.10 to 0.25% by weight of magnesium stearate.  
     
     
         6 . A powder according to  claim 5  wherein the carrier particles are coated with 0.25% by weight of magnesium stearate.  
     
     
         7 . A powder according to  claim 4  wherein magnesium stearate is a crystalline or amorphous material.  
     
     
         8 . A powder according to  claim 4  wherein magnesium stearate is of animal or vegetal origin.  
     
     
         9 . A powder according to  claim 1  wherein the carrier particles comprise one or more crystalline sugars.  
     
     
         10 . A powder according to  claim 1  wherein the carrier particles are α-lactose monohydrate.  
     
     
         11 . A powder according to  claim 1  wherein the carrier particles have a particle size which lies between 20 and 1000 μm.  
     
     
         12 . A powder according to  claim 11  wherein the carrier particles have a particle size which lies between 90 and 150 μm.  
     
     
         13 . A powder according to  claim 1  wherein at least 50% of the lubricant has a particle size more than 4 μm.  
     
     
         14 . A powder according to  claim 1  wherein the lubricant is magnesium stearate and has a specific surface area which lies in the range 0.5-1.5 m 2 g measured by Malvern.  
     
     
         15 . A powder according to  claim 1  wherein the active ingredient has a particle size less than 10 μm, preferably less than 6 μm.  
     
     
         16 . A powder according to  claim 1  wherein the active ingredient includes a steroid.  
     
     
         17 . A powder according to  claim 14  wherein the active ingredient is beclomethasone dipropionate or budesonide and its epimers or flunisolide.  
     
     
         18 . A powder according to  claim 1  wherein the active ingredient includes a β 2 -agonist selected from salbutamol, formoterol, salmeterol, terbutaline and their salts.  
     
     
         19 . A powder according to  claim 18  wherein the active ingredient includes salbutamol base.  
     
     
         20 . A carrier for use in a powder according to  claim 1  made of carrier particles and up to 0.5% by weight of lubricant particles.  
     
     
         21 . A carrier according to  claim 20  wherein the lubricant particles at least partially coat the surface of the carrier particles.  
     
     
         22 . A method for producing the carrier according to  claim 21 , the method including the step of mixing the carrier particles with up to 0.5% by weight of lubricant thereby coating the highest as possible percentage of carrier particles surface, thus achieving an increase of the fine particle dose.  
     
     
         23 . A method according to  claim 22  wherein the carrier particles and lubricant particles are mixed for between 2 min. and 480 min.  
     
     
         24 . A method according to  claim 22  wherein the carrier particles and lubricant particles are mixed using a rotating body mixer or a stationary body mixer with a rotating mixing blade or a high-speed mixer.  
     
     
         25 . A method according to  claim 22  wherein the mixer is a tumbling blender rotating at 5-100 r.p.m.  
     
     
         26 . A method according to  claim 22  wherein the coated carrier particles have a water contact angle of at least 30°.