How to circumvent untoward drug crystallization during emulsion-templated microencapsulation process

Abstract

Unwanted drug crystals often form on the surface of PLGA microspheres or in an aqueous phase when a hydrophobic drug undergoes emulsion-templated microencapsulation processes. In our study, over 70% of progesterone crystallizes in the aqueous phase when microencapsulation proceeds with a typical oil-in-water solvent evaporation process. During filtration employed for microsphere recovery, unentrapped drug crystals are collected alongside with progesterone-containing microspheres. This phenomenon accompanies unfavorable consequences on the microsphere quality. In contrast, when microspheres are prepared with a new solvent extraction-evaporation hybrid process, it is possible to completely avoid drug crystallization. Consequently, the new microencapsulation technique yields high drug encapsulation efficiencies of >= 90.8%, and the resultant microspheres show a homogeneous size distribution pattern. Also, the microsphere surface is free of drug crystals. For loading hydrophobic drugs into PLGA microspheres, the new microencapsulation process reported in this study has distinct advantages over commonly used emulsion-templated solvent evaporation processes. (C) 2016 Wiley Periodicals, Inc.