Residual solvent extraction method and microparticles produced thereby

Abstract

Methods for preparing microparticles having reduced residual solvent levels. Microparticles are contacted with a non-aqueous washing system to reduce the level of residual solvent in the microparticles. Preferred non-aqueous washing systems include 100% ethanol and a blend of ethanol and heptane. A solvent blend of a hardening solvent and a washing solvent can be used to harden and wash microparticles in a single step, thereby eliminating the need for a post-hardening wash step.

1 . Microparticles for the sustained release of exendin, the microparticles prepared by the process comprising: 
 a) combining an aqueous phase comprising exendin and sucrose with an oil phase comprising poly(d,l-lactic-co-glycolic acid) 5050 DL 4A polymer in methylene chloride to form an emulsion;    b) combining the emulsion with a coacervation agent to form embryonic microparticles, wherein the coacervation agent is silicone oil;    c) transferring the embryonic microparticles to a quench solvent to harden the microparticles, wherein the quench solvent is a 90:10 heptane:ethanol mixture;    d) collecting the hardened microparticles; and    e) drying the hardened microparticles.