目的制备人参皂苷Rh₂自微乳释药系统并进行评价,为人参皂苷Rh₂口服制剂的开发提供参考。方法测定人参皂苷Rh₂在各种油相、乳化剂和助乳化剂中的溶解度,选择溶解度较大的溶剂进行组合,采用伪三元相图法研究不同油相、乳化剂和助乳化剂形成微乳的能力和区域,绘制不同处方组成的相图,以自微乳化的时间、乳滴粒径、形成微乳的外观,载药量为指标,进一步筛选处方,找出最佳的组合和处方配比并进行体外溶出度和大鼠在体小肠吸收的评价。结果在人参皂苷Rh₂自微乳处方中,以油酸乙酯(油相)、聚山梨酯-80(乳化剂)、Transcutol P(助乳化剂)和Labrafil M1944CS(油相)、聚山梨酯-80(乳化剂)、Transcutol P(助乳化剂)组成的两种处方可以获得较好的自乳化效果。其最佳处方比例为Labrafil M1944CS-Tween80-Transcutale=30∶40∶30;Ethyl Oleate-Tween80-Tanscutal P=30∶45∶25。两种自微乳释药系统胶囊的溶出速度明显优于普通胶囊,SMEDDS的小肠吸收呈一级速率过程,吸收速率常数显著高于人参皂苷Rh₂溶液(P<0.01),SMEDDS在2h的吸收百分率为56.8%,明显高于人参皂苷Rh₂溶液(P<0.05)。说明SMEDDS可以改善人参皂苷Rh₂的小肠吸收。结论SMEDDS可有效增加人参皂苷Rh₂的溶解度,明显改善体外溶出度,增加大鼠小肠吸收。

OBJECTIVE To prepare and evaluate self-microemulsifying drug delivery system(SMEDDS)of containing ginsenoside Rh2 for improving the in vitro drug dissolution and enhancing the in vivo drug absorption.METHODS The solubility of ginsenoside Rh2 was determined in various vehicles including oil,surfactant and cosurfactant.The oil,surfactant and cosurfactant with high solubility of ginsenoside were formulated and emulsified in aqueous media under conditions of gentle agitation.Pseudo-ternary phase diagrams were constructed to identify the efficient self-microemulsification region.Particle size,self-microemulsification time,appearance and amount of loading drug were determined.The optimized formulations were obtained and in vitro dissolution and the rats small intestines in situ were evaluated.RESULTS Two composition with larger self-microemulsification region in Pseudo-ternary phase diagrams were Labrafil M 1944 CS /Tween80/Transcutal P and Ethyl Oleate/Tween80/Transcutal.The optimized formulations were Labrafil M 1944 CS /Tween80/Transcutal P(30∶40∶30)and Oleate/Tween80/Transcutal P(30∶45∶25).The release rate of ginsenoside Rh₂ from two capsules with SMEDDS was significantly higher than the capsules with original powder.The absorption rate in rat small intestines of ginsenoside Rh₂ from SMEDDS were significantly higher than that of Micell solution and SMEDDS.The absorption was increased by 1.7 fold compared with Micell solution.CONCLUSION SMEDDS were potential drug carrier for ginsenoside Rh₂ in oral administration for improving solubility,dissolution and absorption in small intestines