Critical effect of freezing/freeze-drying on sustained release of FITC-dextran encapsulated within PLGA microspheres

Critical effect of freezing/freeze-drying on sustained release of FITC-dextran encapsulated within PLGA microspheres
March 2004
Tae Hyoung Kim and Tae Gwan Park
International Journal of Pharmaceutics, Volume 271, Issues 1-2, 1 March 2004, Pages 207-214
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Abstract
The cause of initial burst release of hydrophilic macromolecular drugs from biodegradable polymeric microspheres was identified. Poly(Image,Image-lactic-co-glycolic acid) microspheres encapsulating fluorescein isothiocyanate (FITC)-labled dextran was prepared by a double emulsion solvent evaporation method. The extent of initial burst release was examined by varying the formulation process conditions such as solvent evaporation, washing, freezing, and freeze-drying. Confocal microscopy was employed to analyze the underlying mechanism of burst release. The extent of burst release was gradually reduced after the repeated washing of embryonic microspheres before freeze-drying, indicating that FITC-dextran molecules entrapped within unhardened microspheres were slowly diffused out. However, freezing and subsequent drying processes of the embryonic microspheres resulted in much increased extent of burst release, suggesting that the initial burst release was primarily caused by the rapid diffusion of FITC-dextran through the microporous channels. Confocal microscopic analysis revealed that the freeze-drying process generated water-escaping micro-channels, through which the encapsulated molecules were presumably dumped out. Vacuum-drying was a good alternative choice in reducing the initial burst, compared to freeze-drying.