The aim of this study was to develop a formulation to improve the oral absorption of baicalin(BA)by combining a phospholipid complex(PC)and self-emulsifying microemulsion drug delivery system(SMEDDS),termed BA–PC–SMEDDS.BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage(CP).The physicochemical properties of BA–PC were determined.The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model.The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model.The CP of BA–PC reached 100%when the molar ratio of drug to phospholipid(PP)was Z1:1.The solubility of BA–PC increased in both water and octanol,and the log P o/w of BA–PC was increased significantly.BA–PC–SMEDDS could be dispersed more evenly in water,compared to BA and BA–PC.Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA,while improved significantly in BA–PC–SMEDDS.The relative bioavailability of BA–PC(1:2)–SMEDDS was 220.37%.The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.
Huiyi WuXiaoying LongFei YuanLi ChenSujing PanYunjun LiuYoshiko StowellXiaoling Li
目的探索葛根素自微乳给药系统(self-microemulsifying drug delivery systems of puerarin,PUE-SMEDDS)对PUE经肠淋巴转运及其口服生物利用度的影响。方法构建SD大鼠肠系膜淋巴转运模型,口服给药后同步收集淋巴液和血样,HPLC色谱法测定PUE在淋巴液和血浆中的含量,用梯形面积法计算AUC。结果葛根素混悬液(PUE-Suspension)的淋巴转运相对较低,Cmax仅为0.39μg·m L-1,而PUE-SMEDDS的Cmax为5.77μg·m L-1,显著提高PUE肠淋巴转运(P<0.001)。PUE-Suspension在淋巴液和血浆中的AUC0-12 h分别为158.1,438.1 min·μg·m L-1,淋巴转运量占体内吸收总量的36.09%;而PUE-SMEDDS在淋巴液和血浆中的AUC0-12 h分别为1953.3,1641.3 min·μg·m L-1,淋巴转运量占体内吸收总量的54.34%,PUE-SMEDDS的相对生物利用度(Fr)为603.0%。结论 SMEDDS能同时促进PUE经淋巴转运和血液吸收,显著提高PUE的口服生物利用度,而且PUE的淋巴转运量大于血液循环。
