Drug Particles From Freezing Onto A Surface

Abstract

The present invention is a method for preparing micron-sized or submicron-sized drug particles comprising contacting a solution comprising a poorly water soluble drug substance and at least one freezable organic solvent with a cold surface so as to freeze the solution; and removing the organic solvent. The resulting particles are also disclosed, as are several embodiments of an apparatus that can be used in performing the method of the present invention.

1 .- 4 . (canceled) 
     
     
         5 . The drug particles according to  claim 15  wherein the cold surface is cooled using a cryogenic solid, a cryogenic gas, a cryogenic liquid or a heat transfer fluid capable of reaching cryogenic temperatures. 
     
     
         6 . The drug particles according to  claim 15  wherein the freezable organic solvent is selected from the group consisting of alcohols, ethers, halocarbons, hydrocarbons, halogenated hydrocarbons, aromatic hydrocarbons, esters, acetates, organic acids, amines, ketones, sulfones, nitrites, carbonates, and combinations thereof. 
     
     
         7 .- 10 . (canceled) 
     
     
         11 . The drug particles according to  claim 15  wherein the solution further comprises at least one stabilizer. 
     
     
         12 . The drug particles according to  claim 11  wherein the stabilizer is selected from the group consisting of phospholipids, surfactants, polymeric surfactants, vesicles, polymers, including copolymers and homopolymers and biopolymers, dispersion aids, and combinations thereof. 
     
     
         13 . The drug particles according to  claim 15  wherein step (e) is performed using sublimation or evaporation. 
     
     
         14 . (canceled) 
     
     
         15 . Drug particles produced by a method which comprises:
 (a) cooling a cold solid surface to less than 5° C.;   (b) selecting a freezable organic solvent with a freezing point close to the temperature of the cold surface and into which a poorly water soluble drug substance dissolves;   (c) dissolving the poorly water soluble drug substance in the freezable organic solvent into a solution;   (d) contacting the solution with the cold solid surface so as to freeze the solution, wherein the rate of freezing of the solution is determined by the difference between the freezing point of the freezable organic solvent and the temperature to which the cold solid surface is cooled in step (a); and   (e) removing the organic solvent, wherein the resulting particles have a mean volume average particle size from less than 0.05 microns to 24 microns, a surface area of at least 2 m 2 /g and exhibit an in vitro dissolution rate of at least 1.5 times better than that of the unprocessed drug.   
     
     
         16 .- 17 . (canceled) 
     
     
         18 . A pharmaceutical formulation comprising:
 drug particles according to  claim 15 ; and   a pharmaceutically-acceptable carrier.   
     
     
         19 . (canceled)