去甲基斑蝥酸钠脂质微球体内外评价

目的制备去甲基斑蝥酸钠脂质微球并对其体外各项性质及大鼠体内药代动力学特征进行研究。方法 分别采用动态光散射法、HPLC法和反向透析技术考察了制剂的粒径、 ζ-电位、含量、包封率、体外不同介质中的释放特性及以不同介质稀释后样品的性质变化等对制剂做出较全面的体外质量评价。以去甲基斑蝥酸钠注射液为参比制剂，HPLC-MS法测定了大鼠体内药代动力学。结果制剂各项理化性质较好，平均粒径约为200 nm， ζ-电位为-38 mV，含量约100%，包封率约85%。在pH 7.8的PBS中药物1 h释放约50%，4 h释放约85%以上。以葡萄糖注射液稀释样品的粒径、 ζ-电位值变化较小，以5倍量稀释时制剂在2 h内的包封率可保持在80%以上。单剂量股静脉注射脂质微球的药代动力学参数AUC为111.28 μg·mL^-1·h^-1，血药浓度数据符合双隔室模型。实验表明本制剂与注射液体内各项血浆药代动力学参数无明显差异。结论脂质微球各项性质较理想且并未改变药物体内血浆药代动力学特征。

In vitro and in vivo assesemet of sodium norcantharidin lipid microsphere

AIM: To prepare lipid microsphere of sodium norcantharidin (NCTD) and then study their characters and pharmacokinetic behavior. METHODS: Dynamic Light Scattering, HPLC and retrodialysis technique were used to determine the in vitro characters of the NCTD loaded lipid microsphere (LM), such as the particle size, xi-potential, content, incorporation ratio, release profile and changes after dilute. And the plasma concentration was determined by HPLC-MS, compared with NCTD aqueous solution at the same time. RESULTS: Every property showed that the LM was preferable. The average diameter was about 200 nm. The xi-potential was - 38 mV. The content was close to 100%. And the incorporation ratio exceeded 80%. After i. v. administration of single dose, the pharmacodynamic parameter of LM AUC was 111.28 microg x mL(-1) x h(-1). The data of plasma concentrations showed that the NCTD LM was of two compartment. There was no obvious difference between in vivo parameters of LM and reference solution. CONCLUSION: The NCTD LM was eligible and the character of it in vivo was not changed.