Inhalable Powder Containing Tiotropium

Abstract

The invention relates to powdered preparations containing tiotropium for inhalation, processes for preparing them as well as their use in preparing a pharmaceutical composition for the treatment of respiratory complaints, particularly for the treatment of COPD (chronic obstructive pulmonary disease) and asthma.

1 . An inhalable powder comprising 0.04 to 0.8% of tiotropium in admixture with a physiologically acceptable excipient, characterised in that the excipient consists of a mixture of coarser excipient with an average particle size of 15 to 80 μm and finer excipient with an average particle size of 1 to 9 μm, the proportion of the finer excipient constituting 1 to 20% of the total amount of excipient. 
   
   
       2 . An inhalable powder according to  claim 1 , characterised in that the tiotropium is present in the form of the chloride, bromide, iodide, methanesulphonate, para-toluenesulphonate or methyl sulphate thereof. 
   
   
       3 . An inhalable powder comprising between 0.048 and 0.96% of tiotropium bromide in admixture with a physiologically acceptable excipient, characterised in that the excipient consists of a mixture of coarser excipient with an average particle size of 15 to 80 μm and finer excipient with an average particle size of 1 to 9 μm, the proportion of the finer excipient constituting 1 to 20% of the total amount of excipient. 
   
   
       4 . An inhalable powder comprising between 0.05 and 1% of tiotropium bromide monohydrate in admixture with a physiologically acceptable excipient, characterised in that the excipient consists of a mixture of coarser excipient with an average particle size of 15 to 80 μm and finer excipient with an average particle size of 1 to 9 μm, the proportion of the finer excipient constituting 1 to 20% of the total amount of excipient. 
   
   
       5 . An inhalable powder according to one of  claims 1 ,  2 ,  3  or  4 , characterised in that the excipient consists of a mixture of coarser excipient with an average particle size of 17 to 50 μm and finer excipient with an average particle size of 2 to 8 μm. 
   
   
       6 . An inhalable powder according to one of  claims 1 ,  2 ,  3  or  4 , characterised in that the proportion of finer excipient in the total amount of excipient is 3 to 15%. 
   
   
       7 . An inhalable powder according to one of  claims 1 ,  2 ,  3  or  4 , characterised in that the tiotropium used has a mean particle size of 0.5 to 10 μm. 
   
   
       8 . An inhalable powder according to one of  claims 1 ,  2 ,  3  or  4 , characterised in that one or more monosaccharides, disaccharides, oligo- or polysaccharides, polyalcohols, salts thereof, or mixtures thereof are used as the excipients. 
   
   
       9 . An inhalable powder according to  claim 8 , characterised in that glucose, arabinose, lactose, saccharose, maltose, dextrane, sorbitol, mannitol, xylitol, sodium chloride, calcium carbonate or mixtures thereof are used as the excipients. 
   
   
       10 . An inhalable powder according to  claim 9 , characterised in that glucose or lactose or mixtures thereof are used as the excipients. 
   
   
       11 . A process for preparing an inhalable powder according to one of  claims 1  to  4 , comprising: (a) mixing coarser excipient fractions with finer excipient fractions to obtain an excipient mixture, and (b) mixing the excipient mixture thus obtained with the tiotropium. 
   
   
       12 . An inhalable powder prepared by the process according to  claim 11 . 
   
   
       13 . A method of treating a disease that is responsive to the administration of tiotropium, comprising administering to a host in need thereof an inhalable powder according to one of  claims 1  to  4  or  12 . 
   
   
       14 . A method according to  claim 13 , wherein the disease is asthma or COPD. 
   
   
       15 . An inhalette capsule containing an inhalable powder according to one of  claims 1  to  4  orb  12 . 
   
   
       16 . An inhalette capsule containing from 3 to 10 mg of inhalable powder according to one of  claims 1  to  4  or  12 . 
   
   
       17 . An inhalette capsule according to  claim 16 , containing between 1.2 and 80 μg of tiotropium.