Key parameters affecting the initial release (burst) and encapsulation efficiency of peptide-containing poly(lactide-co-glycolide) microparticles.

摘要

The objective of this study was to identify key variables affecting the initial release (burst) and the encapsulation of leuprolide acetate-containing poly(lactide-co-glycolide) (PLGA) microparticles, which were prepared by the cosolvent evaporation method. Adjusting parameters, which affected the PLGA precipitation kinetics, provided efficient ways to increase the encapsulation efficiency and to control the initial release. Addition of 0.05M NaCl to the external aqueous phase increased the encapsulation efficiency and the initial release; in contrast, NaCl at high concentration (0.5M) delayed polymer precipitation and resulted in non-porous microparticles with a low initial release. The presence of ethanol in the external phase led to porous microparticles with an increased initial release but a decreased encapsulation efficiency. The initial release also decreased with decreasing volume of the external phase and homogenization speed, as well as with covering the preparation apparatus; however, these variations had no significant effect on the encapsulation efficiency. Scale-up of the laboratory size by a factor of 5 and 25 showed insignificant influence on the encapsulation efficiency, particle size, and drug release.