Residual solvent extraction method and microparticles produced thereby
View Patent ↗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. A method for preparing microparticles, comprising:
preparing a first phase comprising an active agent; a biodegradable, biocompatible polymer; and a solvent;
preparing a continuous second phase with which the first phase is substantially immiscible;
combining the first phase and the second phase to form an emulsion;
extracting the solvent from the emulsion with an extraction medium, to form microparticles containing the active agent; and
washing the microparticles with a non-aqueous washing system comprising ethanol to thereby reduce the level of residual solvent.
2. The method of claim 1 , wherein the active agent is selected from risperidone, 9-hydroxyrisperidone, and pharmaceutically acceptable salts of the foregoing.
3. The method of claim 1 , wherein the polymer is selected from poly(glycolic acid), poly(d,l-lactic acid), poly(l-lactic acid), and copolymers of the foregoing.
4. The method of claim 3 , wherein the polymer is poly(d,l-lactic-co-glycolic acid).
5. The method of claim 1 , wherein the solvent comprises a blend of ethyl acetate and benzyl alcohol.
6. The method of claim 1 , wherein the extraction medium comprises ethyl acetate.
7. The method of claim 1 , wherein the non-aqueous washing system is 100% ethanol.
8. The method of claim 1 , wherein the first phase comprises risperidone, poly(d,l-lactic-co-glycolic acid), and a blend of ethyl acetate and benzyl alcohol,
wherein the extraction medium comprises ethyl acetate, and
wherein the non-aqueous washing system is 100% ethanol.
9. The method of claim 8 , wherein the second phase comprises polyvinyl alcohol and ethyl acetate.
10. The method of claim 1 , further comprising:
rinsing the washed microparticles with water; and
final drying of the rinsed microparticles.
11. Microparticles prepared by the method of claim 1 .
12. Microparticles prepared by the method of claim 9 .