不同粒径波棱甲素纳米混悬剂的制备及药动学研究

目的 制备不同粒径波棱甲素纳米混悬剂(herpetrione nanosuspension,Her-NS),并探讨粒径对Her-NS 口服生物利用度的影响.方法 采用反溶剂沉淀法制备2种不同粒径Her-NS,采用单因素实验以平均粒径、多分散系数、稳定性指数为评价指标优化处方工艺参数,扫描电子显微镜(SEM)观察Her-...

Preparation and in vivo pharmacokinetic behaviors of herpetrione nanosuspensions

Objective To prepare herpetrione nanosuspension (Her-NS) with different particle sizes, and explore the effects of particle size on the oral bioavailability. Methods Her-NS with two different particle sizes were prepared by anti-solvent precipitation method, and optimized by single factor experiments with average particle size, polydispersity index, and stability index as evaluation indexes. The morphology of Her-NS was observed by scanning electron microscope (SEM), and the physical state was analyzed by X-ray diffraction (XRD). The drug release of Her-NS was evaluated by dialysis method. The oral pharmacokinetics of Her-NS with two different particle sizes were compared using SD rats. Results Her-NS with two different particle sizes around 200 nm (Her-NS₂₀₀) and 450 nm (Her-NS₄₅₀) were successfully prepared with P188 and P407 as stabilizers. SEM showed that Her-NS with two different particle sizes were all spherical in shape, and the XRD analysis showed that Her-NS with two different particle sizes were amorphous. In vitro release and pharmacokinetic results showed that the cumulative release and the C_max and AUC_0-t of Her-NS with two different particle sizes were significantly increased as compared to coarse Her, but the C_max and AUC_0-t of the Her-NS₂₀₀ were higher than those of Her-NS₄₅₀. Conclusion NS can significantly improve the oral bioavailability of Her, and the small particle size is more significant.