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目的制备ISA胆盐/磷脂混合胶束,并对其体外释放特性和大鼠体内药动学特征进行研究。方法采用薄膜水化法制备ISA胆盐/磷脂混合胶束,以星点设计-效应面法优化处方,透析法考察其体外释放行为,大鼠灌胃给药考察其体内药动学特征。结果优化所得ISA胆盐/磷脂混合胶束药物浓度为0.87 mg.mL-1,包封率为86.34%,载药量为4.87%,平均粒径为148.3 nm;经拟合ISA胆盐/磷脂混合胶束释放行为符合Rither-Peppas方程;药动学数据经房室模型拟合,ISA与ISA胆盐/磷脂混合胶束均符合二室模型,与原药组相比,胶束组吸收速度常数增加,达峰时间缩短,消除半衰期延长,分布体积减小,清除率降低,AUC增大,MRT延长。结论 ISA胆盐/磷脂混合胶束可增加药物溶解度,提高生物利用度。
OBJECTIVE To prepare ISA bile salt / phospholipid mixed micelles and study its in vitro release characteristics and pharmacokinetics in rats. Methods ISA bile salt / phospholipid micelles were prepared by membrane hydration method. The in vitro release behavior was investigated by star design-response surface methodology and dialysis method. The rats were intragastrically administrated to investigate their pharmacokinetic characteristics. Results The drug concentration of ISA bile salt / phospholipid mixed micelles was 0.87 mg.mL-1, the encapsulation efficiency was 86.34%, the drug loading was 4.87% and the average particle size was 148.3 nm. The mixed micelle release behavior was in accordance with the Rither-Peppas equation. Pharmacokinetic data were fitted by atrioventricular model, ISA and ISA bile salt / phospholipid mixed micelles were in accordance with the two-compartment model, compared with the original drug group, micellar group absorption rate Increase of constant, peak time shortened, elimination of half-life extension, distribution volume decreases, clearance rate decreased, AUC increased, MRT prolonged. Conclusion ISA bile salt / phospholipid mixed micelles can increase drug solubility and improve bioavailability.