大黄素固体分散体制备、表征与释药机制研究

Study on Preparation, Characterization and Drug Release Mechanism of Emodin Solid Dispersion

关键词:  大黄素  固体分散体  分子对接  热熔挤出  释药机制

Key words:  emodin  solid dispersion  molecular docking  hot melt extrusion  drug release mechanism

摘要:

目的 制备大黄素固体分散体,提高其体外溶出度并探究其释药机制。方法 采用分子对接技术,辅助筛选聚合物载体。以大黄素为原料药,Kollidon^® VA64为聚合物载体,采用热熔挤出工艺制备大黄素固体分散体。通过溶出仪测定其体外溶出,利用SEM、DCS和PXRD对原料药和固体分散体的表面形态和晶型进行表征,最后采用FTIR、NMR和分子动力学模拟对固体分散体的释药机制进行探究。结果 相较于大黄素原料药,大黄素固体分散体在4种介质中的溶出被明显改善,大黄素由结晶态转化为无定形态,药物与聚合物载体间形成了氢键。结论 固体分散体中药物晶型的转变和氢键的产生是改善药物体外溶出的主要因素。

Abstract:

OBJECTIVE To prepared the emodin solid dispersion and to improve its dissolution in vitro and explore its drug release mechanism. METHODS Molecular docking was used to assist in screening polymer carriers. Emodin solid dispersion was prepared by hot melt extrusion using emodin as raw material and Kollidon^® VA64 as polymer carrier. The in vitro dissolution rate of the solid dispersions was measured by stripping apparatus. SEM, DCS and PXRD were used to characterize the surface morphology and crystal shape of the raw material and solid dispersion. Finally, FTIR, NMR and molecular dynamics simulation were used to explore the drug release mechanism of solid dispersions. RESULTS Compared with emodin bulk drug, the dissolution rate of emodin solid dispersion in four buffers was significantly improved, and emodin was transformed from crystalline state to amorphous form, and hydrogen bond was formed between drug and polymer carrier. CONCLUSION The crystal transformation of drug and the generation of hydrogen bond in solid dispersion are the main factors to improve drug dissolution in vitro.