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目的制备普罗布考混合胶束(Probucol loaded mixed micelles,PMM)用于提高其口服生物利用度。方法选择磷脂、脱氧胆酸钠为辅料,以共沉淀法制备普罗布考混合胶束(PMM),并对其体外理化特性以及体内药动学行为进行评价。结果制备了普罗布考混合胶束,其优化处方组成为磷脂︰脱氧胆酸钠︰普罗布考(3︰4︰1)。PMM平均粒径为82.28 nm,多分散系数为0.179,药物主要以非晶型状态存在于PMM中。大鼠体内药动学研究表明,与原料药相比,口服PMM后,普罗布考的峰浓度和口服生物利用度分别提高了2.28倍和4.43倍。结论混合胶束能够显著提高普罗布考的口服生物利用度,为解决难溶性药物的口服吸收问题提供了一种有效策略。
Objective To prepare Probucol loaded mixed micelles (PMM) for improving its oral bioavailability. Methods Phospholipid and sodium deoxycholate were used as excipients to prepare probucol mixed micelles (PMM) by coprecipitation method. The physical and chemical properties and pharmacokinetic behavior of probucol mixed micelles were evaluated. Results The probucol mixed micelles were prepared and the optimized formulation consisted of phospholipid: sodium deoxycholate: probucol (3︰4︰1). The average particle size of PMM was 82.28 nm, and the polydispersity index was 0.179. The drug existed mainly in amorphous state in PMM. Pharmacokinetic studies in rats showed that peak concentrations of oral probucol and oral bioavailability were 2.28 and 4.43 times higher, respectively, when compared to APIs after oral administration of PMM. Conclusion The mixed micelles can significantly increase the oral bioavailability of probucol, providing an effective strategy for the oral absorption of insoluble drugs.