调释型蛇床子素固体分散体的制备、表征及体外释放研究  

Preparation,characterization,and in vitro release of modified-release osthole solid dispersions

作　　者：王梦颜 高丹 杨岚[1] 任娅博 刘喜纲[1] 王汝兴[1] 常金花[1] 王迎寒[1] WANG Mengyan;GAO Dan;YANG Lan;REN Yabo;LIU Xigang;WANG Ruxing;CHANG Jinhua;WANG Yinghan(Hebei(Chengde)Industrial Technology Institute of Chinese Medicinal Materials,Chengde Medical University,Chengde 067000,China)

机构地区：[1]河北省(承德)中药材产业技术研究院,承德医学院,河北承德067000

出　　处：《中草药》2025年第6期1979-1988,共10页Chinese Traditional and Herbal Drugs

基　　金：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。

摘　　要：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 p

关 键 词：蛇床子素 固体分散体 醋酸羟丙甲基纤维素琥珀酸酯 尤特奇L100 表征 体外释放 

分 类 号：R283.6[医药卫生—中药学]