TY - JOUR
T1 - Critical effect of freezing/freeze-drying on sustained release of FITC-dextran encapsulated within PLGA microspheres
AU - Kim, Tae Hyoung
AU - Park, Tae Gwan
PY - 2004/3/1
Y1 - 2004/3/1
N2 - The cause of initial burst release of hydrophilic macromolecular drugs from biodegradable polymeric microspheres was identified. Poly(D,L-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.
AB - The cause of initial burst release of hydrophilic macromolecular drugs from biodegradable polymeric microspheres was identified. Poly(D,L-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.
KW - Biodegradable polymer
KW - Burst release
KW - Freezing/freeze-drying
KW - Microspheres
UR - http://www.scopus.com/inward/record.url?scp=1142309793&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2003.11.021
DO - 10.1016/j.ijpharm.2003.11.021
M3 - Article
C2 - 15129987
AN - SCOPUS:1142309793
SN - 0378-5173
VL - 271
SP - 207
EP - 214
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -