茴三硫固体分散体的体内外评价

In Vitro and in Vivo Evaluation of Anethole Trithione Solid Dispersions

关键词:  茴三硫  固体分散体  热熔挤出  溶出度  生物利用度

Key words:  anethole trithione  solid dispersion  hot-melt extrusion  dissolution rate  bioavailability

摘要:

目的 采用热熔挤出技术制备茴三硫固体分散体，用于提高其溶出度和口服生物利用度。方法 以水溶性聚合物Plasdone S630为载体，用热熔挤出技术制备茴三硫固体分散体。采用差示扫描量热法和X射线粉末衍射法对固体分散体进行表征，并评价其溶出度及犬体内药动学行为。结果 药物以无定形或分子状态存在于固体分散体中，溶出速率明显高于参比制剂与物理混合物，在40 ℃，湿度75%加速6个月，溶出曲线和固体分散体中茴三硫存在状态未发生变化。犬体内药动学研究结果表明，茴三硫固体分散体的Cmax和口服生物利用度是参比制剂的1.66倍和1.57倍。结论 采用热熔挤出技术制备的茴三硫固体分散体为热力学稳定体系，能明显提高茴三硫的体外溶出度和口服生物利用度。

Abstract:

OBJECTIVE To development anethole trithione(ATT) solid dispersion with high dissolution and bioavailability using hot-melt extrusion. METHODS Solid dispersion with carrier of Plasdone S630 was preparaed by hot-melt extrusion and then characterized by differential sacanning calorimetry(DSC), X-ray powder diffraction(XRPD), in vitro dissolution test, and in vivo bioavailability study. RESULTS ATT exited as amorphous or molecular state in solid state that could be proved by DSC and XRPD. The dissolution rate of ATT was significantly accelerated. The dissolution profile and the solid state properties of the product were maintained after storage at 40 ℃, 75% RH for 6 months. The results of pharmacokinetics in beagles showed that the Cmax and AUC of ATT solid dispersions were 1.66 times and 1.57 times high than reference preparation. CONCLUSION ATT solid dispersion preparaed by hot-melt extrusion is thermodynamically stable system. The dissolution in vitro and bioavailability in beagle dogs after oral administration is markedly improved.