Powder formulations containing tiotropium suitable for inhalation

Abstract

A method of making a physically stable and homogenous powdered pharmaceutical composition comprising a tiotropium salt and a physiologically acceptable excipient, the method comprising: (a) suspending the tiotropium salt and the physiologically acceptable excipient in a suspending agent in which the tiotropium salt and the physiologically acceptable excipient are essentially insoluble to obtain a suspension; and (b) removing the suspending agent from the suspension of step (a) to obtain the pharmaceutical composition, the pharmaceutical composition itself, and method of treating respiratory diseases, especially chronic obstructive pulmonary disease and asthma, in a patient in need thereof by administering an effective amount of the pharmaceutical composition to the patient.

1 - 14 . Cancelled  
     
     
         15 . A physiologically stable and homogenous powdered pharmaceutical composition comprising a tiotropium salt and a physiologically acceptable excipient obtainable by a method comprising: 
 (a) suspending the tiotropium salt and the physiologically acceptable excipient in a suspending agent in which the tiotropium salt and the physiologically acceptable excipient are essentially insoluble to obtain a suspension; and    (b) removing the suspending agent from the suspension of step (a) to obtain the pharmaceutical composition.    
     
     
         16 . The pharmaceutical composition according to  claim 15 , wherein the tiotropium salt is the chloride, bromide, iodide, methanesulfonate, p-toluenesulfonate, or methylsulfate salt.  
     
     
         17 . The pharmaceutical composition according to  claim 16 , wherein the physiologically acceptable excipient is selected from the group consisting of a monosaccharide, disaccharide, oligo- or polysaccharide, polyalcohol, or a salt.  
     
     
         18 . The pharmaceutical composition according to  claim 17 , wherein the physiologically acceptable excipient is selected from the group consisting of glucose, arabinose, lactose, saccharose, maltose, trehalose, dextrane, sorbitol, mannitol, xylitol, sodium chloride, or calcium carbonate.  
     
     
         19 . The pharmaceutical composition according to  claim 15  which contains tiotropium in an amount of 0.001% to 2% of the composition.  
     
     
         20 . The pharmaceutical composition according to  claim 19 , wherein the tiotropium salt is the chloride, bromide, iodide, methanesulfonate, p-toluenesulfonate, or methylsulfate salt.  
     
     
         21 . The pharmaceutical composition according to  claim 20 , wherein the physiologically acceptable excipient is selected from the group consisting of a monosaccharide, disaccharide, oligo- or polysaccharide, polyalcohol, or a salt.  
     
     
         22 . The pharmaceutical composition according to  claim 21 , wherein the physiologically acceptable excipient is selected from the group consisting of glucose, arabinose, lactose, saccharose, maltose, trehalose, dextrane, sorbitol, mannitol, xylitol, sodium chloride, or calcium carbonate.  
     
     
         23 . A physically stable and homogenous powdered pharmaceutical composition comprising a tiotropium salt and a physiologically acceptable excipient obtainable by a method comprising: 
 (a) adding a first portion of suspending agent to tiotropium salt to obtain a suspension;    (b) mixing and optionally sonically treating the suspension of step (a);    (c) adding a physiologically acceptable excipient to the suspension of step (b);    (d) adding another portion of suspending agent to the suspension of step (c);    (e) mixing and optionally sonically treating the suspension of step (d);    (f) removing the suspending agent from the suspension of step (e) to obtain a residue; and    (g) drying the residue to obtain the pharmaceutical composition.    
     
     
         24 . The pharmaceutical composition according to  claim 23 , wherein the tiotropium salt is the chloride, bromide, iodide, methanesulfonate, p-toluenesulfonate, or methylsulfate salt.  
     
     
         25 . The pharmaceutical composition according to  claim 24 , wherein the physiologically acceptable excipient is selected from the group consisting of a monosaccharide, disaccharide, oligo- or polysaccharide, polyalcohol, or a salt.  
     
     
         26 . The pharmaceutical composition according to  claim 25 , wherein the physiologically acceptable excipient is selected from the group consisting of glucose, arabinose, lactose, saccharose, maltose, trehalose, dextrane, sorbitol, mannitol, xylitol, sodium chloride, or calcium carbonate.  
     
     
         27 . A method of treating respiratory diseases in a patient in need thereof, the method comprising administering to the patient an effective amount of the pharmaceutical composition according to  claim 15 .  
     
     
         28 . The method of  claim 27 , wherein the respiratory disease is asthma or COPD.  
     
     
         29 . A method of treating respiratory diseases in a patient in need thereof, the method comprising administering to the patient an effective amount of the pharmaceutical composition according to  claim 19 .  
     
     
         30 . The method of  claim 29 , wherein the respiratory disease is asthma or COPD.  
     
     
         32 . A method of treating respiratory diseases in a patient in need thereof, the method comprising administering to the patient an effective amount of the pharmaceutical composition according to  claim 23 .  
     
     
         33 . The method of  claim 32 , wherein the respiratory disease is asthma or COPD.