Methods and systems for polymer precipitation and generation of particles

Abstract

Processes for precipitating polymers from a polymer-containing solution are disclosed.

What is claimed is: 
     
         1 . A process for precipitating a cyclodextrin-containing polymer (CDP) -camptothecin conjugate, from a polymer-containing solution, the process comprising: providing a vessel containing a volume of a cooled non-solvent; agitating the cooled non-solvent; introducing the polymer-containing solution into the cooled non-solvent to form a mixture comprising a liquid and the CDP-camptothecin conjugate; and maintaining the mixture under conditions to precipitate at least a portion of the CDP-camptothecin conjugate, from the mixture, thereby precipitating at least a portion of the CDP-camptothecin conjugate. 
     
     
         2 . The process of  claim 1 , wherein the CDP-camptothecin conjugate is CRLX101. 
     
     
         3 . The process of  claim 1 , wherein the mixture is maintained at a temperature of about −50 to about −100 degrees Celsius. 
     
     
         4 . The process of  claim 1 , further comprising removing at least a portion of the liquid from the vessel subsequent to precipitation of the CDP-camptothecin conjugate, thereby separating the precipitated CDP-camptothecin conjugate, from the mixture. 
     
     
         5 . The process of  claim 1 , wherein the precipitated CDP-camptothecin conjugate is filtered at a temperature of about −50 degrees Celsius to about −100 degrees Celsius. 
     
     
         6 . The process of  claim 5 , wherein the filtered precipitated CDP-camptothecin conjugate is stored in the cooled non-solvent. 
     
     
         7 . The process of  claim 1 , wherein the cooled non-solvent comprises acetone. 
     
     
         8 . The process of  claim 1 , wherein the temperature of the cooled non-solvent is from about −50 to about −100 degrees Celsius. 
     
     
         9 . The process of  claim 8 , wherein the temperature of the cooled non-solvent is about −78 degrees Celsius. 
     
     
         10 . A process for generating particles, comprising:
 providing a vessel containing a cooled non-solvent; agitating the cooled non-solvent; introducing a polymer-containing solution comprising a CDP-camptothecin conjugate into the cooled non-solvent to form a mixture comprising a liquid and the CDP-camptothecin conjugate; and maintaining the mixture under conditions to precipitate at least a portion of the CDP-camptothecin conjugate from the mixture, thereby precipitating at least a portion of the CDP-camptothecin conjugate; and isolating at least a portion of the precipitated CDP-camptothecin conjugate; and suspending the precipitated CDP-camptothecin conjugate in an aqueous solution, thereby generating particles.   
     
     
         11 . The process of  claim 10 , wherein the CDP-camptothecin conjugate is CRLX101. 
     
     
         12 . The process of  claim 10 , wherein the pH of the aqueous solution is from about 2 to about 6. 
     
     
         13 . The process of  claim 10 , wherein the cooled non-solvent comprises methanol, ethanol, acetone, n-propanol, isopropanol, n-butanol, ethyl ether, methyl isobutyl ketone or ethyl acetate or a combination thereof. 
     
     
         14 . The process  claim 10 , further comprising filtering the particles. 
     
     
         15 . The process of  claim 14 , further comprising collecting the particles. 
     
     
         16 . The process of  claim 15 , further comprising lyophilizing the collected particles. 
     
     
         17 . A plurality of particles generated according to the process of  claim 10 . 
     
     
         18 . The plurality of particles of  claim 17 , wherein the particles are nanoparticles. 
     
     
         19 . A preparation comprising the CDP-camptothecin conjugate precipitated by the process of  claim 1 . 
     
     
         20 . The preparation of  claim 19 , wherein the CDP-camptothecin conjugate is CRLX101. 
     
     
         21 . A system for precipitating a CDP-camptothecin conjugate from a polymer-containing solution, the system comprising:
 a vessel for containing a fluid, the vessel having at least one input port and an output port;   a cooling system in communication with the vessel configured to cool and maintain the temperature of the fluid in the vessel;   wherein said input port is configured to allow introduction of the polymer-containing solution into the vessel to precipitate at least a portion of the CDP-camptothecin conjugate.