【作者】 刘俊； 邱利焱； 金一；

【Author】 LIU Jun, QIU Li-yan and JIN Yi Institute of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031

【机构】 浙江大学药学院；

【摘要】 目的:制备黄芩素-羟丙基-β-环糊精共冻干物,增强黄芩素的溶出性能,提高生物利用度。方法采用溶液法制备黄芩素和羟丙基-β-环糊精复合物,冷冻干燥得黄色固体。以DSC和XRD等方法测定共冻干物的理化性质。转篮法比较兆冻干物和黄芩素原料药的溶出性能。大鼠分别静脉注射或灌胃给予黄芩素-羟丙基-β-环糊精共冻干物或黄芩素原料药,用 RP-HPLC方法同时测定不同时间血浆中黄芩素及其主要有效代谢产物黄芩苷的含量,通过DAS 2．0统计分析软件计算药动学参数。结果研究表明黄芩素-羟丙基-β-环糊精共冻干物显示了区别于结晶性原料黄芩素的无定形性质。在45 min内黄芩素-羟丙基-β-环糊精共冻干物和黄芩素原料药的溶出度分别为103．2％和0．9％。大鼠灌胃给予黄芩素-羟丙基-β- 环糊精共冻干物或黄芩素原料药后,以其主要有效代谢产物黄芩苷计,其AUC0-∞分别为15707．4和9516．9 nmol·min·mL-1, tmax分别为7．5和90．0 min,Cmax分别为33．8和16．6 nmol·mL-1。结论黄芩素-羟丙基-β-环糊精共冻干物为无定形固体粉末,其良好的溶出性能提高了黄芩素的口服生物利用度。更多还原

【Abstract】 OBJECTIVE To prepare baicalein-hydroxypropyl-β-cyclodextrin co-lyophilized powder and study its improved dissolution and bioavailability properties. METHODS The complex of baicalein and hydroxypropyl-β-cyclodextrin was prepared in solution and its solids system was prepared by freeze-drying method. Co-lyophilized powder was characterized by DSC and XRD. Comparison of the dissolution properties between the co-lyophilized powder and free baicalein was performed. The concentration of baicalein and its mainly conjugated metabolite, baicalin in rat plasma after intravenous or oral administration was determined by RP-HPLC method. The pharmacokinetics parameters were computed by soft program DAS 2.0. RESULTS Experiment results showed that the baicalein and hydroxypropyl-β-cyclodextrin co-lyophilized powder was amorphous and showed a significant improved dissolution rate in comparison to free baicalein for 103.2% to 0.9% in 45 minutes. After oral dosing co-lyophilized powder or free drug, the pharmacokinetics parameters of the mainly conjugated metabolite, baicalin were respectively AUC0-β 15707.4 and 9516.9 nmol·min·mL-1, tmax 7.5 and 90.0 min, Cmax 33.8 and 16.6 nmol·mL-1. CONCLUSION It was concluded that the dissolution and bioavailability properties of baicalein - hydroxypropyl-β-cyclodextrin co-lyophilized amorphous powder improved significantly in comparison the crystal baicailein.更多还原