目的 分别采用4种载体制备蛇床子素固体分散体（osthole solid dispersions，Ost-SDs），旨在调控蛇床子素口服后释放部位和释放度。方法 分别以醋酸羟丙甲基纤维素琥珀酸酯（hydroxypropyl methylcellulose acetate succinate，HPMCAS，H、M、L型）和尤特奇L100（Eudragit L100，EL100）为载体，采用溶剂蒸发法制备Ost-SDs，以在0.1 mol/L盐酸水溶液和pH 6.8磷酸盐缓冲液（PBS）中的累积溶出率为考察指标，筛选Ost-SDs药载比，确定最优处方；分别采用扫描电子显微镜（scanning electron microscope，SEM）、傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）、X射线粉末衍射分析（X-ray powder diffraction analysis，XRD）、差示扫描量热分析（differential scanning calorimetry，DSC）和偏振光显微镜（polarized light microscopy，PLM）等方法表征其形貌和物理化学性质；通过进行水接触角、平衡溶解度和体外释放试验，评价Ost-SDs的体外水溶性。结果Ost-SDs的优选处方为以无水乙醇-二氯甲烷（1∶1）混合溶液为溶剂，蛇床子素质量浓度为0.6 mg/mL，药载比为1∶7；在4种载体制备的Ost-SDs中，蛇床子素的晶型均为无定型；Ost-SDs的FTIR图表明蛇床子素和载体之间能够形成分子间氢键；蛇床子素原料药和物理混合物（Ost-PMs）中的蛇床子素，在PLM下均能够观察到明显的双折射现象，而在Ost-SDs中，蛇床子素基本没有双折射现象；Ost-SDs的水接触角低于Ost-PMs，表明其水润湿性增强；Ost-SDs在pH 6.8 PBS中的溶解度是蛇床子素原料药的156%～193%；而且Ost-SDs在含有0.1%聚山梨酯80的盐酸水溶液中，蛇床子素在2 h的累积释放率低于Ost-PMs，而在pH 6.8 PBS中，其累积释放度高于Ost-PMs。结论 以HPMCAS（H、M、L型）和EL100为载体，采用溶剂蒸发法能够成功制备Ost-SDs，而且4种Ost-SDs均能够保证蛇床子素在模拟胃液中少量释放，同时提高蛇床子素在模拟小肠液中的释放速率和累积释放率。

Objective A total of four carriers were used to prepare osthole solid dispersions (Ost-SDs), aiming to regulate the release site and release rate after oral administration of osthole. Methods The Ost-SDs were prepared by solvent evaporation method using hydroxypropyl methylcellulose acetate succinate (HPMCAS, H, M and L) and Eudragit L100 (EL100) as carriers, respectively; and the drug-loading ratio was screened and the optimal prescription was determined using the accumulated dissolution rate in 0.1 mol/L aqueous hydrochloric acid and pH 6.8 phosphate buffer solution (PBS) as the index; the morphology and physicochemical properties of Ost-SDs were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction analysis (XRD), differential scanning calorimetry (DSC) and polarized light microscopy (PLM); and the water solubility of the Ost-SDs was evaluated by performing aqueous contact angle, equilibrium solubility, and in vitro release tests. Results The optimum formulation of Ost-SDs was as follow: the mixture solution of anhydrous ethanol-dichloromethane (1:1) as solvent, osthole concentration of 0.6 mg/mL, and drug-loading ratio of 1:7; the crystalline form of osthole was amorphous in the Ost-SDs prepared in the study; and FTIR of the Ost-SDs demonstrated that intermolecular hydrogen bonding could be formed between the osthole and the carrier; both crude osthole and the physical mixtures (Ost-PMs) were observed obvious birefringence phenomenon under PLM, while Ost-SDs were basically free of birefringence phenomenon; the water contact angle of Ost-SDs was lower than that of the Ost-PMs, which indicated its enhanced water wettability; in comparison with crude osthole, the solubility of Ost-SDs in pH 6.8 PBS was 156% to 193%; and the accumulated dissolution rate of osthole of Ost-SDs at 2 h was lower than that of Ost-PMs in aqueous hydrochloric acid solution containing 0.1% Tween 80, but higher than that of Ost-PMs in pH 6.8 PBS. Conclusion The solvent evaporation method was able to successfully prepare Ost-SDs using HPMCAS (H, M, L types) and EL100 as carriers, and all the four Ost-SDs prepared in the study reduced the dissolution of osthole in simulated gastric fluid and improve the dissolution rate and cumulative dissolution rate of osthole in simulated small intestinal fluid.

R283.6

河北省自然科学基金资助（H2022406073）；河北省高等学校科学技术研究项目资助（ZD2020154）；河北省中央引导地方科技发展资金项目（246Z2504G）；河北省（承德）中药材产业技术研究院开放性课题资助；承德医学院中药学学科建设项目