应用实验设计优化制备适于口服的聚酯微球

采用双乳溶剂蒸发法制备包裹蛋白质的聚酯微球 ,蛋白质包裹率大于 80 %。应用均匀设计和正交设计试验研究了 8种因素对微球粒径的影响。结果表明 ,粒径主要受有机相中聚合物浓度和外水相中稳定剂浓度的影响。通过二次回归组合设计 ,建立了微球平均粒径与聚合物浓度及稳定剂浓度之间的数学关系式。根据此式 ,选择不同的聚合物浓度和稳定剂浓度可制备适于蛋白质口服给药的微球。

Optimized preparation of polyester microspheres for oral administration using an experimental design

The poly(DL-lactide-co-glycolide) (PLG)microspheres entrapping proteins have been prepared using a water-in-oil-in-water (W 1/O/W 2) emulsification-solvent evaporation technique,and the entrpping efficiency was above 80%. A uniform design and an orthogonal design were applied to investigate the influence on the microsphere size of sundry process variables: the concentration of protein in the W 1 phase, the concentration of PLG in the O phase, the concentration of PVA stabilizer in the W 2 phase, the concentration of surfactant in the O phase , the mixing time during preparing the primary emulsion (W 1/O), the volume ratio of the W 1 phase and the O phase, the stirring rate during the process of secondary emulsification , and the homogenisation time in this stage. The concentrations of PLG and PVA were found to strongly affect the microsphere size. The regression equation between the size and the two variables was obtained by a rotatable central composite design. According to the mathematical model, it is possible to easily deduce experimental conditons to prepare microspheres with the desired properties for oral administration.