Apparatus and method for preparing microparticles

Abstract

Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.

1 . A method for controlling particle size distribution of microparticles, comprising: 
 preparing a first phase, the first phase comprising an active agent and a polymer;    preparing a second phase;    preparing a quench liquid;    pumping the first phase and the second phase through a manifold that includes a plurality of static mixers to form an emulsion;    flowing the emulsion into the quench liquid whereby droplets of the emulsion form microparticles; and    adjusting a residence time of the emulsion in the manifold to obtain a predetermined particle size distribution of the resulting microparticles, wherein the residence time is equal to a length of the manifold divided by an average velocity of the emulsion through the manifold.    
     
     
         2 . The method of  claim 1 , wherein the adjusting step is carried out to increase the residence time, thereby narrowing particle size distribution.  
     
     
         3 . The method of  claim 1 , wherein the adjusting step is carried out to decrease the residence time, thereby broadening particle size distribution.  
     
     
         4 . The method of  claim 1 , wherein the manifold comprises a plurality of individual static mixers configured so that the emulsion flows sequentially through the plurality of individual static mixers.  
     
     
         5 . The method of  claim 1 , wherein the adjusting step is carried out by changing the length of the manifold.  
     
     
         6 . The method of  claim 1 , wherein the adjusting step is carried out by changing the velocity of the emulsion in the manifold.  
     
     
         7 . The method of  claim 1 , wherein the residence time is from 3 to 4 seconds.  
     
     
         8 . The method of  claim 1 , wherein the residence time is less than one second.  
     
     
         9 . The method of  claim 1 , wherein the manifold comprises a scissors mixing element.  
     
     
         10 . The method of  claim 1 , wherein the manifold comprises a helical mixing element.  
     
     
         11 . The method of  claim 1 , wherein the manifold comprises a layered mixing element.  
     
     
         12 . A method for controlling particle size distribution of microparticles, comprising: 
 combining a first phase and a second phase in a manifold to form an emulsion, wherein the manifold comprises a plurality of static mixers and the first phase comprises an active agent and a polymer;    flowing the emulsion into an extraction liquid for extracting the solvent from the emulsion to form microparticles; and    adjusting a residence time of the emulsion in the manifold to obtain a predetermined particle size distribution of the resulting microparticles, wherein the residence time is equal to a length of the manifold divided by an average velocity of the emulsion through the manifold.    
     
     
         13 . The method of  claim 12 , wherein the adjusting step is carried out to increase the residence time, thereby narrowing particle size distribution.  
     
     
         14 . The method of  claim 12 , wherein the adjusting step is carried out to decrease the residence time, thereby broadening particle size distribution.  
     
     
         15 . The method of  claim 12 , wherein the manifold comprises a plurality of individual static mixers configured so that the emulsion flows sequentially through the plurality of individual static mixers.  
     
     
         16 . The method of  claim 12 , wherein the adjusting step is carried out by changing the length of the manifold.  
     
     
         17 . The method of  claim 12 , wherein the adjusting step is carried out by changing the velocity of the emulsion in the manifold.  
     
     
         18 . The method of  claim 12 , wherein the residence time is from 3 to 4 seconds.  
     
     
         19 . The method of  claim 12 , wherein the residence time is less than one second.  
     
     
         20 . The method of  claim 12 , wherein the manifold comprises a scissors mixing element.  
     
     
         21 . The method of  claim 12 , wherein the manifold comprises a helical mixing element.  
     
     
         22 . The method of  claim 12 , wherein the manifold comprises a layered mixing element.  
     
     
         23 . A method for controlling particle size distribution of microparticles, comprising: 
 combining a first phase and a second phase in a static mixing assembly to form an emulsion, wherein the first phase comprises an active agent, a polymer, and a solvent;    flowing the emulsion into an extraction liquid for extracting the solvent from the emulsion to form microparticles; and    adjusting a velocity of the emulsion through the static mixing assembly to obtain a predetermined droplet size, wherein an average velocity of the emulsion is equal to a length of the static mixing assembly divided by the residence time of the emulsion in the static mixing assembly.    
     
     
         24 . The method of  claim 23 , wherein the adjusting step is carried out to increase the droplet size, thereby broadening particle size distribution.  
     
     
         25 . The method of  claim 23 , wherein the adjusting step is carried out to decrease the droplet size, thereby narrowing particle size distribution.  
     
     
         26 . The method of  claim 23 , wherein the static mixing assembly comprises a plurality of individual static mixers configured so that the emulsion flows sequentially through the plurality of individual static mixers.  
     
     
         27 . The method of  claim 23 , wherein the adjusting step is carried out by changing the length of the static mixing assembly.  
     
     
         28 . The method of  claim 23 , wherein the static mixing assembly comprises a scissors mixing element.  
     
     
         29 . The method of  claim 23 , wherein the static mixing assembly comprises a helical mixing element.  
     
     
         30 . The method of  claim 23 , wherein the static mixing assembly comprises a layered mixing element.