Inhalable imatinib formulations, manufacture, and uses thereof

Abstract

The invention relates to inhalable imatinib formulations, manufacture, and uses thereof.

1 - 9 . (canceled) 
     
     
         10 . A method of preparing an inhalable formulation comprising:
 micronizing imatinib freebase particles;   suspending micronized imatinib freebase particles in a solution; and   spray drying the suspended micronized imatinib freebase particles,   wherein the micronized imatinib freebase particles in the inhalable formulation have a mass median aerodynamic diameter in the range of about 0.5 m to about 5 m.   
     
     
         11 . The method of  claim 10 , wherein the inhalable formulation comprises less than 5% water. 
     
     
         12 . The method of  claim 10 , wherein the imatinib freebase particles in the inhalable formulation are crystalline. 
     
     
         13 . The method of  claim 12 , wherein the imatinib freebase particles are type A crystals. 
     
     
         14 . The method of  claim 10 , wherein one or more excipients are included in the suspending step. 
     
     
         15 . The method of  claim 14 , wherein at least one of the one or more excipients is a water-soluble excipient selected from the group consisting of leucine, dileucine, trileucine, trehalose, mannitol, citrate, and acetate. 
     
     
         16 . The method of  claim 14 , wherein at least one of the one or more excipients is a water insoluble excipient selected from the group consisting of lecithin, distearoylphosphatidylcholine (DSPC). 
     
     
         17 . The method of  claim 10 , wherein the inhalable formulation contains a therapeutically effective amount of imatinib freebase for treating a condition of pulmonary cardiovascular system. 
     
     
         18 . The method of  claim 17 , wherein the condition of the pulmonary cardiovascular system is pulmonary arterial hypertension (PAH). 
     
     
         19 . The method of  claim 12 , wherein the inhalable formulation comprises less than 5% amorphous imatinib particles by mass. 
     
     
         20 . The method of  claim 12 , wherein the inhalable formulation comprises less than 3% amorphous imatinib freebase particles by mass. 
     
     
         21 . The method of  claim 12 , wherein the inhalable formulation comprises less than 1% amorphous imatinib freebase particles by mass. 
     
     
         22 . The method of  claim 12 , wherein inhalable formulation comprises less than 1% water. 
     
     
         23 . The method of claim  1 , wherein greater than 95% of the imatinib in the inhalable formulation is present in a single crystal form. 
     
     
         24 . The method of  claim 23 , wherein the imatinib freebase single crystal form is type A crystal.