Process for preparing solid amorphous particles comprising tiotropium bromide and a co-solid

Abstract

A method of making an inhalable medicament is provided, in particular a new solid-state form of tiotropium bromide. The medicament can be in the form of solid amorphous particles containing an intimate admixture of tiotropium bromide together with a pharmaceutically acceptable co-solid having a glass transition temperature of at least − 50. degree. C., such as a sugar and/or sugar alcohol.

What is claimed is: 
     
         1 . A process for preparing solid amorphous particles of tiotropium bromide comprising lyophilizing an aqueous solution of tiotropium bromide together with a pharmaceutically acceptable co-solid having a glass transition temperature of at least −50° C. 
     
     
         2 . The process as claimed in  claim 1 , wherein the co-solid has a water solubility of at least 20 mg per 100 mL, at 20° C. 
     
     
         3 . The process as claimed in  claim 1 , wherein the co-solid comprises at least one of a sugar and a sugar derivative. 
     
     
         4 . The process as claimed in  claim 3 , wherein the co-solid comprises the sugar derivative and the sugar derivative is a sugar polyol or an amino sugar. 
     
     
         5 . The process as claimed in  claim 3 , wherein the co-solid comprises the sugar and the sugar is a monosaccharide or a disaccharide. 
     
     
         6 . The process as claimed in  claim 3 , wherein the co-solid is selected from the group consisting of glucose, lactose, mannitol, mannose, sucrose, trehalose and combinations thereof. 
     
     
         7 . A process as claimed in  claim 1 , further comprising, after lyophilizing, micronizing the particles. 
     
     
         8 . A process as claimed in  claim 1 , wherein the particles formed have a particle size of 1-10 microns. 
     
     
         9 . A process for preparing solid amorphous particles of tiotropium bromide comprising freeze-drying an aqueous solution of tiotropium bromide and lactose by spraying droplets of the solution into liquid nitrogen to form the particles. 
     
     
         10 . The process of  claim 9  wherein said droplets are about 10 μm. 
     
     
         11 . The process of  claim 9  further comprising collecting and placing the particles in a vacuum freezer for 24 hours. 
     
     
         12 . The process of  claim 10  wherein the resulting particles are suitable for inhalation.