槲皮素纳米乳的制备及药代动力学研究

Preparation of Quercetin Nanoemulsion and Its Pharmacokinetics in Rats

目的制备槲皮素纳米乳(QT-NE),进行处方优化及体外质量评价,并考察其在大鼠体内的药代动力学行为。方法通过溶解度试验、相容性研究及伪三元相图的绘制初步设计QT-NE处方;在此基础上以粒径和多分散系数为考察指标,采用星点设计-效应面法筛选出最优处方并进行外观、类型、形态、粒径以及体外溶出的考察;大鼠灌胃给予槲皮素(QT)原料药和QT-NE,比较其口服药代动力学差异。结果最终确定QT-NE的最优处方为油酸乙酯-吐温80-PEG 400-水=7.3%:23.2%:6.8%:62.7%。所制得的QT-NE外观澄清透明,为O/W型纳米乳;在电镜下呈较规则类圆球形,粒径为(13.06±0.50)nm,分散系数为0.207±0.008;体外溶出度与药动学结果显示,与QT原料药比较,QT-NE的累积溶出度在24 h内明显提高,QT-NE的达峰浓度(C_(max))、药时曲线下面积(AUC_(0-t))均显著提高(P<0.01)。结论QT-NE制备工艺简单,可有效提高QT的生物利用度。

Objective To develop quercetin nanoemulsion(QT-NE)and evaluate its pharmacokinetics in rats.Methods The formulation of QT-NE was optimized by the solubility test,compatibility study,pseudo-ternary phase diagram and central composite design-response surface method,respectively.The optimized QT-NE was characterized by the visual appearance,type,morphology,particle size and in vitro dissolution.The pharmacokinetics of the optimized QT-NE was also evaluated in rats and compared with raw quercetin(QT).Results The optimized formulation of QT-NE consisted of ethyl oleate,Twcen-80,PEG 400 and water at the ratio of 7.3%:23.2%:6.8%:62.7%.The QT-NE had a clear and transpar ent visible appearance and O/W type nanoemulsion.The morphology of QT-NE was nearly spherical under a transmission electron microscope.The particle size and polydispersity index were (13.06±0.50)nm and 0.207±0.008,respectively.The results of in vitro dissolution and pharmacokinetic studies showed that the amount of cumulative dissolution,C_(max),and AUC_(0-t)of QT from QT-NE were significantly enhanced(P<0.01)compared with raw QT.Conclusion The preparation process of QT-NE is simple and can effectively improve the oral bioavailability of QT.