阿苯达唑固体分散体体外溶出和大鼠体内药动学研究

Dissolution behavior in vitro and pharmacokinetic profile of albendazole solid dispersion in rats

目的:研究阿苯达唑(ABZ)固体分散体体外溶出以及体内药动学规律。方法:固体分散体的制备采用溶剂法;采用3种方程对溶出度数据进行拟合,并比较固体分散体及3个参比样品溶出度情况;采用HPLC法测定大鼠血浆药物浓度,考察ABZ固体分散体在大鼠体内药动学规律。结果:在20min时固体分散体、市售片剂、简单混合物及原料药的溶出度分别达到:92.8%,76.5%,40.8%和2.9%,溶出规律均符合Weibull模型。大鼠体内药动学研究结果表明:固体分散体与市售片剂相比Cmax和AUC均有很大提高;采用隔室模型和统计矩2种模型进行计算固体分散体相对生物利用度,均能达到230%。结论:固体分散体可以显著提高阿苯达唑(ABZ)体外溶出及体内吸收。

Objective：To evaluate the albendazole （ABZ） solid dispersion dissolution behavior of A BZ in vitro and pharmacokinetics of the rats. Methods ： ABZ solid dispersion was carried out by solvent-evaporation method. The dissolution results were fitted by three functions, and the dissolution behavior of solid dispersion and other three samples was studied. The plasma concentrations were determined by HPLC and pharmacokinetic behaviors were evaluated in rats. Results： The dissolved amount from solid dispersion at 20min was much higher（ 92.8% ）than that of the market tablet（ 76.5% ） , simple mixture（ 40.8% ）and raw material. The accumulative release percentage of all of them was described by Weibull function. The area under the curve （AUC） and C were significantly higher in solid dispersion group than that in the market tablet. The calculation results by both compartment model and statistical moment model were the same, and the relative bioavailability of solid dispersion was 230 percent. Conclusion：The solid dispersion system can improve ABZ dissolution in vitro and absorption in vivo significantly.