甘草酸胆盐/磷脂混合胶束微丸的制备及其体外评价

Preparation and in vitro Evaluation of Glycyrrhizin Bile Salt/phosphatidylcholine Mixed-micelles Pellets

目的制备甘草酸胆盐/磷脂混合胶束微丸,并对其进行体外肠吸收评价。方法采用薄膜分散法制备混合胶束,进一步利用流化床包衣技术固化胶束溶液,并通过正交试验优化微丸处方,装入肠溶胶囊;采用大鼠肠外翻模型考察肠吸收。结果优选处方为PVP-K30 4%、包衣增重25%、药物浓度15.2 mg·ml-1,测得的收率为(94.19±2.33)%,复溶后的胶束粒径为(167.98±1.42)nm,人工胃液2 h的释放量为(5.29±1.62)%,人工肠液45 min释放量为(84.76±3.14)%。肠外翻吸收实验显示固化载药胶束与载药胶束溶液相比,各时间点累积吸收量差异不大。结论采用流化床底喷工艺制备甘草酸胆盐/磷脂混合胶束微丸,工艺简单可行,质量稳定可控。

Objective To prepare glycyrrhizin bile salt/phosphatidylcholine mixed-micelles （GL-SDC/ PL-MMs） pellets and to evaluate their intestinal absorption. Methods GL-SDC/PL-MMs were produced using a film dispersion method and solidified by fluid bed spray coating technology. The optimal formulation of GL-SDC/PL-MMs pellets was obtained by orthogonal design. The intestinal absorption of the pellets was investigated using in vitro everted gut scas. Results The yield of GL-SDC/PL-MMs pellets prepared by optimized formulation （4% PVP-K30, 25% coating weight, 15.2 mg·ml-1 drug concentration） was （94.19 ± 2.33 ）%, the particle size obtained of reconsti- tuted MMs from pellets was （ 167.98 ± 1.42） nm, and the release of the optimal formulation was （ 84.76 ±3.14） % in artificial intestinal liquid within 45 min, but was （5.29 ± 1.62） % in artificial gastric liquid within 2 h. There was no significant difference between the absorption profiles of GL-SDC/PL-MMs solution and pellets in the intestinal absorp- tion study. Conclusion It is simple and feasible to solidify glycyrrhizin bile salt/phosphatidylcholine mixed-micelles pellets by bottom-spray fluid bed technology,and its quality is stable and under control.