不同制备工艺对薯蓣皂苷元固体分散体体外溶出、物相特征、体内药动学的影响  

Effects of different preparation processes on in vitro dissolution, phase characteristics and in vivo pharmacokinetics of diosgenin solid dispersions

作　　者：刘沛[1] 常金花[1] 薛禾菲 王雨欣 徐林 张领 刘翠哲[1] 周剑宇[1] LIU Pei;CHANG Jin-hua;XUE He-fei;WANG Yu-xin;XU Lin;ZHANG Ling;LIU Cui-zhe;ZHOU Jian-yu(Hebei Provincial Key Laboratory for Nerve Injury and Repair,Hebei Provincial Key Laboratory for Research and Development of Chinese Medicine,Chengde Medical University,Chengde 067000,China)

机构地区：[1]承德医学院,河北省神经损伤与修复重点实验室,河北省中药研究与开发重点实验室,河北承德067000

出　　处：《中成药》2023年第2期349-357,共9页Chinese Traditional Patent Medicine

基　　金：河北省高等学校科学技术研究项目(QN2019167,QN2020241);河北省高校重点学科建设项目(冀教高[2013]4号);河北省科技厅“技术创新引导专项-科技工作会商”项目(2020);河北省神经损伤与修复重点实验室开放课题(NJKF202102)。

摘　　要：目的 考察不同制备工艺对薯蓣皂苷元固体分散体体外溶出、物相特征、体内药动学的影响。方法 以Soluplus为载体,分别采用共沉淀法、微波淬冷法、冷冻干燥法制备固体分散体,测定溶解度、溶出度,采用差示扫描量热分析、粉末X射线衍射、扫描电镜、傅里叶红外光谱研究物相特征,拟合水接触角曲线。30只大鼠随机分为5组,分别灌胃给予原料药、物理混合物、3种制备工艺所得固体分散体的0.5%CMC-Na混悬液(100 mg/kg),于0、0.083、0.25、0.5、0.75、1、2、3、4、6、8、12、24、36、48、72 h采血,UPLC-MS/MS法测定薯蓣皂苷元血药浓度,计算主要药动学参数。结果 固体分散体溶解度、120 min内累积溶出度高于原料药,以共沉淀法所得更明显。薯蓣皂苷元以无定形态存在于共沉淀法、微波淬冷法所得固体分散体中,以晶体存在于冷冻干燥法所得固体分散体中。薯蓣皂苷元与Soluplus之间存在相互作用。固体分散体水接触角小于原料药、物理混合物,共沉淀法所得固体分散体的水接触角最小,润湿性最强。共沉淀法、微波淬冷法所得固体分散体的溶解机制为载体控制,冷冻干燥法所得固体分散体的溶解机制为药物控制。与原料药比较,共沉淀法、微波淬冷法所得固体分散体AUC_(0~t)、AUC_(0~∞)、C_(max)升高(P<0.05,P<0.01),CL_(z/F)降低(P<0.01),相对生物利用度分别为576.69%、447.80%。结论 共沉淀法更适合制备薯蓣皂苷元固体分散体。AIM To investigate the effects of different preparation processes on in vitro dissolution, phase characteristics and in vivo pharmacokinetics of diosgenin solid dispersions.METHODS Coprecipitation method, microwave quenching method and freeze-drying method were applied to preparing solid dispersions with Soluplus as a carrier, respectively, after which solubility and dissolution rate were determined, phase characteristics were studied by differential scanning calorimetry, powder X-ray diffraction, scanning electron microscope and fourier transform infrared spectroscopy, the curves for water contact angles were fitted. Thirty rats were randomly assigned into five groups and given intragastric administration of the 0.5%CMC-Na suspensions of raw medicine, physical mixture and solid dispersions obtained by three preparation processes(100 mg/kg), respectively, after which blood collection was made at 0, 0.083, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 h, UPLC-MS/MS was adopted in the plasma concentration determination of diosgenin, and main pharmacokinetic parameters were calculated.RESULTS The solid dispersions demonstrated higher solubility and accumulative dissolution rate within 120 min than the raw medicine, especially for those obtained by coprecipitation method. Diosgenin existed in an amorphous state in the solid dispersions obtained by coprecipitation method and microwave quenching method, and a crystal state in the solid dispersions obtained by freeze-drying method. There was an interaction between diosgenin and Soluplus. The water contact angle of solid dispersions was smaller than that of raw medicine and physical mixture, and the solid dispersions obtained by coprecipitation method demonstrated the smallest water contact angle and the strongest wettability. The dissolution mechanisms of solid dispersions obtained by coprecipitation method and microwave quenching method were carrier-controlled, and that of solid dispersions obtained by freeze-drying method was drug-controlled. Compared with raw

关 键 词：薯蓣皂苷元 固体分散体 制备工艺 体外溶出 物相特征 体内药动学 

分 类 号：R943[医药卫生—药剂学]