Method for preparing microparticles having a selected polymer molecular weight

Abstract

A method for preparing microparticles having a selected polymer molecular weight. The hold time and temperature of a solution containing a nucleophilic compound and a polymer having a starting molecular weight are controlled in order to control the molecular weight of the polymer in the finished microparticle product. In this manner, a selected polymer molecular weight in the finished microparticle product can be achieved from a variety of starting material molecular weights.

What is claimed is:  
     
         1 . Microparticles prepared by a method, comprising: 
 preparing a first phase, the first phase comprising naltrexone, a polymer having a starting molecular weight, and a solvent;    combining the first phase with a second phase to form an emulsion;    extracting the solvent from the emulsion to thereby form microparticles; and    wherein the starting molecular weight of the polymer reduces in the first phase so that a finished microparticle polymer molecular weight is achieved.    
     
     
         2 . The microparticles of  claim 1 , wherein the solvent comprises ethyl acetate.  
     
     
         3 . The microparticles of  claim 1 , wherein the preparing step comprises: 
 dissolving naltrexone in benzyl alcohol to form a first solution;    dissolving the polymer in ethyl acetate to form a second solution; and    combining the first solution and the second solution to form the first phase.    
     
     
         4 . The microparticles of  claim 3 , wherein the naltrexone is naltrexone base anhydrous.  
     
     
         5 . The microparticles of  claim 1 , wherein a theoretical drug loading is in the range of from about 30% to 75%.  
     
     
         6 . The microparticles of  claim 1 , wherein the starting molecular weight is in the range of from about 50 kD to about 250 kD.  
     
     
         7 . The microparticles of  claim 1 , wherein the finished microparticle polymer molecular weight is in the range of from about 10 kD to about 185 kD.  
     
     
         8 . The microparticles of  claim 1 , wherein the polymer is selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of lactide and glycolide.  
     
     
         9 . The microparticles of  claim 8 , wherein the polymer is poly(d,l-lactide-co-glycolide) having a molar ratio of lactide to glycolide in the range of from about 100:0 to about 50:50.  
     
     
         10 . The microparticles of  claim 2 , wherein the solvent further comprises benzyl alcohol.  
     
     
         11 . The microparticles of  claim 1 , wherein the extracting step is carried out using an extraction solution.  
     
     
         12 . The microparticles of  claim 11 , wherein the extraction solution is aqueous.  
     
     
         13 . The microparticles of  claim 11 , wherein the extraction solution comprises a quantity of the solvent.  
     
     
         14 . The microparticles of  claim 1 , wherein the combining step is carried out using a static mixer.  
     
     
         15 . The microparticles of  claim 1 , wherein the method further comprises: 
 cold drying the microparticles.    
     
     
         16 . The microparticles of  claim 15 , wherein the method further comprises prior to the cold drying step: 
 rinsing the microparticles with an ethanol solution.    
     
     
         17 . The microparticles of  claim 15 , wherein the method further comprises after the cold drying step: 
 transferring the microparticles to an ethanol solution.    
     
     
         18 . The microparticles of  claim 17 , wherein the method further comprises after the transferring step: 
 final drying the microparticles.    
     
     
         19 . The microparticles of  claim 2 , wherein the polymer is poly(d,l-lactide-co-glycolide) having a molar ratio of lactide to glycolide of about 75:25 and the naltrexone is naltrexone base anhydrous.  
     
     
         20 . Microparticles prepared by a method, comprising: 
 dissolving naltrexone and a polymer having a starting molecular weight in a solvent to form a first phase;    combining the first phase and an aqueous second phase under the influence of mixing means to form an emulsion;    extracting the solvent from the emulsion to thereby form microparticles; and    wherein the starting molecular weight of the polymer reduces in the first phase so that a finished microparticle polymer molecular weight is achieved.    
     
     
         21 . The microparticles of  claim 20 , wherein a theoretical drug loading is in the range of from about 30% to 75%.  
     
     
         22 . The microparticles of  claim 20 , wherein the starting molecular weight is in the range of from about 50 kD to about 250 kD.  
     
     
         23 . The microparticles of  claim 20 , wherein the finished microparticle polymer molecular weight is in the range of from about 10 kD to about 185 kD.  
     
     
         24 . The microparticles of  claim 20 , wherein the polymer is selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, and copolymers of lactide and glycolide.  
     
     
         25 . The microparticles of  claim 24 , wherein the polymer is poly(d,l-lactide-co-glycolide) having a molar ratio of lactide to glycolide in the range of from about 100:0 to about 50:50.  
     
     
         26 . The microparticles of  claim 20 , wherein the extracting step is carried out using an extraction solution.  
     
     
         27 . The microparticles of  claim 26 , wherein the extraction solution is aqueous.  
     
     
         28 . The microparticles of  claim 26 , wherein the extraction solution comprises a quantity of the solvent.  
     
     
         29 . The microparticles of  claim 20 , wherein the combining step is carried out using a static mixer.  
     
     
         30 . The microparticles of  claim 20 , wherein the polymer is poly(d,l-lactide-co-glycolide) having a molar ratio of lactide to glycolide of about 75:25 and the naltrexone is naltrexone base anhydrous.