Preparation of microparticles having improved flow ability

Abstract

Methods for preparing microparticles having improved flowability to facilitate processing in automated equipment. Microparticles are conditioned so that a flowability index of the microparticles is greater than about 60. The conditioning preferably includes maintaining the microparticles at a conditioning temperature for a period of time. The conditioning can be used with microparticles containing an active agent, and with placebo microparticles, and it is reversible.

1 . A method for processing microparticles to improve flowability, comprising: 
 (a) conditioning the microparticles to form conditioned microparticles, wherein the microparticles comprise a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing, wherein the conditioning is carried out by maintaining the microparticles at a conditioning temperature of about 25° C. for a period of at least about 5 days;    (b) measuring a flowability index of the conditioned microparticles; and    (c) if the flowability index of the conditioned microparticles is not greater than about 60, repeating step (a) until the flowability index of the conditioned microparticles is greater than about 60.    
   
   
       2 . A method for processing microparticles to improve flowability, comprising: 
 (a) selecting a conditioning temperature and a time period for processing the microparticles, wherein the microparticles comprise a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing, and wherein the conditioning temperature is less than a glass transition temperature (T g ) of the polymer;    (b) maintaining the microparticles at the conditioning temperature for the time period to form conditioned microparticles;    (c) measuring a flowability index of the conditioned microparticles;    (d) if the flowability index of the conditioned microparticles is not greater than about 60, adjusting the conditioning temperature and the time period so that the flowability index of the conditioned microparticles is greater than about 60.    
   
   
       3 . A method for processing microparticles to improve flowability, comprising: 
 (a) determining a conditioning temperature and a time period for processing the microparticles, wherein the microparticles comprise a polymer selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of the foregoing, and wherein the conditioning temperature is less than a glass transition temperature (T g ) of the polymer;    (b) maintaining the microparticles at the conditioning temperature for the time period to form conditioned microparticles, wherein a flowability index of the conditioned microparticles at the completion of the maintaining step is greater than about 60.    
   
   
       4 . The method of  claim 3 , wherein the determining step comprises: 
 (i) measuring a flowability index of the microparticles;    (ii) if the flowability index of the microparticles is not greater than about 60, adjusting the conditioning temperature and the-time period so that the flowability index of the microparticles at the completion of the maintaining step is greater than about 60.    
   
   
       5 . The method of  claim 1 , wherein the conditioning step is carried out in a temperature-controlled chamber.  
   
   
       6 . The method of  claim 2 , wherein the maintaining step is carried out in a temperature-controlled chamber.  
   
   
       7 . The method of  claim 3 , wherein the maintaining step is carried out in a temperature-controlled chamber.  
   
   
       8 . The method of  claim 1 , wherein a hardness of the conditioned microparticles is greater than about 0.4 MPa.  
   
   
       9 . The method of  claim 2 , wherein a hardness of the conditioned microparticles is greater than about 0.4 MPa.  
   
   
       10 . The method of  claim 3 , wherein a hardness of the conditioned microparticles is greater than about 0.4 MPa.