1. 上海中医药大学中药学院,上海,201203
2. 杭州青玥医药科技有限公司,浙江,杭州,310007
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王志, 叶贝妮, 冯年平. 大豆苷元固体分散体的制备及生物利用度研究[J]. 上海中医药杂志, 2018,52(9):86-91.
WANG Zhi, YE Beini, FENG Nianping. Preparation and bioavailability of daidzein solid dispersion[J]. Shanghai Journal of Traditional Chinese Medicine, 2018,52(9):86-91.
王志, 叶贝妮, 冯年平. 大豆苷元固体分散体的制备及生物利用度研究[J]. 上海中医药杂志, 2018,52(9):86-91. DOI: 10.16305/j.1007-1334.2018.09.023.
WANG Zhi, YE Beini, FENG Nianping. Preparation and bioavailability of daidzein solid dispersion[J]. Shanghai Journal of Traditional Chinese Medicine, 2018,52(9):86-91. DOI: 10.16305/j.1007-1334.2018.09.023.
目的:制备载大豆苷元(daidzein,DZ)二氧化硅(Aeroperl300 Pharma,AP)固体分散体(DZ-AP),并对其促进大豆苷元口服吸收作用进行体内外评价。 方法:利用均匀设计优化DZ-AP处方;采用差示扫描量热法(DSC)、X射线衍射法(XRPD)进行表征;通过检测其体外累积溶出速率和大鼠体内血药浓度变化评价DZ-AP体内外释药行为,并对DZ-AP固体分散体的稳定性进行考察。 结果:均匀实验设计优化出DZ-AP固体分散体的处方为:大豆苷元100 mg,溶解在3倍量的甲醇中,加入300 mg AP,室温搅拌45 min,旋蒸除去溶剂,减压干燥1 h。DSC和XRPD分析表明药物大部分以无定型的状态存在于固体分散体中。与原料药相比,DZ-AP体外溶出速率显著加快。大鼠药动学数据显示,固体分散体的相对生物利用度是大豆苷元原料药的137.1%。稳定性实验结果表明,DZ-AP在室温及加速条件下放置3个月,大豆苷元的含量、溶出度均未发生明显改变,表明在贮存过程中稳定性良好。 结论:以AP为载体制备DZ-AP固体分散体可有效提高大豆苷元的溶出速率和口服生物利用度。
Objective:To prepare the solid dispersion of daidzein (DZ) colloidal silicon dioxide (Aeroperl 300 Pharma, AP) (DZ-AP), and evaluate its promotion effects on oral absorption of daidzein in vivo and in vitro. MethodsThe formulation of DZ-AP was optimized by uniform design. Both differential scanning calorimetry (DSC) and X-ray diffraction (XRPD) were used to characterize DZ-AP. The cumulative dissolution rates and the changes of plasma concentration in rats were detected to evaluate the drug releasing of DZ-AP in vivo and in vitro, and the stability of DZ-AP solid dispersion was investigated. Results:The formulation of DZ-AP solid dispersion was optimized by uniform design as follows:daidzein 100 mg was dissolved in 3 times amount of methanol, 300 mg APs was added, and stirred at room temperature for 45 minutes, evaporated and dried for 1 hour. The DSC and XRPD results showed that majority of the drug existed in amorphous state. The dissolution rate of DZ-AP was significantly faster than that of the raw drug in vitro. The rat pharmacokinetics data showed that the relative bioavailability of solid dispersion was 137.1 percent of raw daidzein. The results of stability test showed that there were no obvious changes in the content and dissolution of daidzein when DZ-AP was stored at room temperature and acceleration condition for 3 months, which indicated the good stability of DZ-AP during storage. Conclusion:The preparation of DZ-AP solid dispersion with AP as carrier can effectively improve the dissolution rate and oral bioavailability of daidzein.
大豆苷元AEROPERL300 Pharma固体分散体生物利用度
daidzeinAEROPERL 300 Pharmasolid dispersionbioavailability
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