活性氯酚3-氯-3’,4’-二羟基二苯甲酮固体分散体的制备及体外溶出研究

Preparation of an active chlorophenol,3-chloro-3',4'-dihydroxy diphenylmethanone solid dispersion and its dissolution test in vitro

目的制备活性氯酚3-氯-3’,4’-二羟基二苯甲酮(HP46)的固体分散体(solid dispersion,SD),以提高HP46的体外溶解度和溶出度。方法以聚乙烯吡咯烷酮(PVPK30)为载体,吐温(Tween80)为表面活性剂,采用溶剂法制备HP46的固体分散体,优化固体分散体组成,并进行体外溶出研究。运用粉末X-射线衍射(XRD)和差示热量扫描(DSC)分析固体分散体中药物的分散状态。结果 HP46固体分散体组成的最优质量比为HP46-PVPK30-Tween80 1∶3∶1,XRD和DSC结果表明HP46以无定型或分子状态存在于载体中,体外溶解度和溶出速率显著提高,溶解度为1 319.4μg/ml,在20 min内累积溶出率为77.23%,溶解度和溶出度较原料药分别提高约30倍和8倍。结论以PVPK30为载体,加入表面活性剂Tween80,可有效提高HP46的溶解度和溶出度,固体分散体最优质量比为HP46-PVPK30-Tween80 1∶3∶1。

Objective To prepare the solid dispersion of an active chlorophenol-3-chloro-3 ＇,4 ＇-dihydroxy diphenylmethanone（ HP46） for enhancing its solubility and dissolution rate in vitro. Methods Solid dispersion（ SD） of HP46 was prepared with PVPK30 as the carrier and tween80 as the surfactant by solvent method. The composition of HP46 solid dispersion was optimized and the dissolution rate in vitro was studied. Powder X-ray diffraction（ XRD） and differential scanning calorimetry（ DSC） were used to analyze the characteristics of HP46 in solid dispersion. Results The best proportion of HP46 solid dispersion was HP46-PVPK30-Tween80 of 1 ∶ 3 ∶ 1. DSC and XRD showed that HP46 was an amorphous form or molecular state in solid dispersion,and the solubility and dissolution rate of HP46 were significantly improved. The solubility of HP46-PVPK30-Tween80（ 1 ∶ 3 ∶ 1） solid dispersion was 1 319. 4μg /ml,and the cumulative dissolution rate attained to 77. 23% in 20 min. The solubility and cumulative dissolution rate of HP46-PVPK30-Tween80（ 1 ∶ 3 ∶ 1） solid dispersion were respectively increased by nearly 30 folds and 8 folds compared with that of HP46.Conclusion The solubility and dissolution rate of HP46 in solid dispersion could be effectively improved with PVPK30 as the carrier and tween80 as the surfactant. The optimal composition mass ratio of solid dispersion is HP46-PVPK30-Tween80 of 1 ∶ 3 ∶ 1.