Preparation of microparticles having improved flowability

Abstract

Methods for preparing microparticles having improved flowability to facilitate processing in automated equipment. Microparticles are maintained at a conditioning temperature for a period of time. The conditioning temperature and period are selected so that the angle of repose of the microparticles is less than about 28°.

What is claimed is:  
     
         1 . A method for processing a quantity of microparticles, comprising: 
 (a) placing the quantity of microparticles into a container;    (b) maintaining the microparticles at a conditioning temperature for a period of time, wherein the conditioning temperature and the period are selected so that an angle of repose of the quantity of microparticles is less than about 28°.    
     
     
         2 . The method of  claim 1 , further comprising after step (b): 
 (c) transferring at least a portion of the quantity of microparticles into a vial filling machine.    
     
     
         3 . The method of  claim 1 , wherein the conditioning temperature is from about 20° C. to about 25° C.  
     
     
         4 . The method of  claim 3 , wherein the period is at least two days.  
     
     
         5 . The method of  claim 3 , wherein the period is at least five days.  
     
     
         6 . The method of  claim 1 , wherein step (b) comprises: 
 (i) rotating the container.    
     
     
         7 . A method for preparing microparticles having improved flowability, comprising: 
 (a) preparing an emulsion that comprises a first phase and a second phase, wherein the first phase comprises an active agent, a polymer, and a solvent for the polymer;    (b) extracting the solvent from the emulsion to form microparticles containing the active agent;    (c) maintaining the microparticles at a conditioning temperature for a period of time, wherein the conditioning temperature and the period are selected so that an angle of repose of the microparticles is less than about 28°.    
     
     
         8 . The method of  claim 7 , wherein step (b) comprises: 
 (i) transferring the emulsion to a solvent extraction medium.    
     
     
         9 . The method of  claim 7 , further comprising prior to step (c): 
 (d) washing the microparticles; and    (e) drying the microparticles.    
     
     
         10 . The method of  claim 7 , wherein step (c) is carried out in a temperature-controlled chamber.  
     
     
         11 . The method of  claim 7 , wherein the conditioning temperature is less than a glass transition temperature (T g ) of the polymer.  
     
     
         12 . The method of  claim 1 , wherein the microparticles comprise a polymer and the conditioning temperature is less than a glass transition temperature (T g ) of the polymer.  
     
     
         13 . The method of  claim 7 , wherein the conditioning temperature is from about 20° C. to about 25° C.  
     
     
         14 . The method of  claim 7 , wherein the active agent is selected from the group consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts thereof.  
     
     
         15 . The method of  claim 14 , wherein the solvent comprises benzyl alcohol and ethyl acetate.  
     
     
         16 . The method of  claim 7 , wherein the polymer is selected from the group consisting of poly(glycolic acid), poly-d,1-lactic acid, poly-1-lactic acid, and copolymers of the foregoing.  
     
     
         17 . The method of  claim 14 , wherein the polymer is selected from the group consisting of poly(glycolic acid), poly-d,1-lactic acid, poly-1-lactic acid, and copolymers of the foregoing.  
     
     
         18 . A method for preparing microparticles having improved flowability, comprising: 
 (a) preparing an emulsion that comprises a first phase and a second phase, wherein the first phase comprises an active agent, a polymer, and a solvent for the polymer;    (b) extracting the solvent from the emulsion to form microparticles containing the active agent;    (c) introducing the microparticles into a container; and    (d) maintaining the container at a conditioning temperature for a period of time, wherein the conditioning temperature and the period are selected so that an angle of repose of the microparticles is less than about 28°.    
     
     
         19 . The method of  claim 18 , wherein step (d) comprises: 
 (i) rotating the container.    
     
     
         20 . Microparticles having improved flowability prepared by a method, comprising: 
 (a) preparing an emulsion that comprises a first phase and a second phase, wherein the first phase comprises an active agent, a polymer, and a solvent for the polymer;    (b) extracting the solvent from the emulsion to form microparticles containing the active agent; and    (c) allowing crystal growth of active agent present on a surface of the microparticles.    
     
     
         21 . The microparticles of  claim 20 , wherein step (c) comprises: 
 (i) maintaining the microparticles at a conditioning temperature for a period of time, wherein the conditioning temperature and the period are selected so that an angle of repose of the microparticles is less than about 28°.    
     
     
         22 . The microparticles of  claim 21 , wherein the conditioning temperature is less than a glass transition temperature (T g ) of the polymer.  
     
     
         23 . The method of  claim 18 , wherein the conditioning temperature is less than a glass transition temperature (T g ) of the polymer.  
     
     
         24 . The microparticles of  claim 21 , wherein the conditioning temperature is from about 20° C. to about 25° C.  
     
     
         25 . The microparticles of  claim 20 , wherein the active agent is selected from the group consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts thereof.  
     
     
         26 . The microparticles of  claim 25 , wherein the solvent comprises benzyl alcohol and ethyl acetate.  
     
     
         27 . The microparticles of  claim 20 , wherein the polymer is selected from the group consisting of poly(glycolic acid), poly-d,1-lactic acid, poly-1-lactic acid, and copolymers of the foregoing.