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共晶技术提高黄芩素溶出度及生物利用度的研究

周生研, 张博文, 魏元锋, 钱帅, 张建军, 高缘

周生研, 张博文, 魏元锋, 钱帅, 张建军, 高缘. 共晶技术提高黄芩素溶出度及生物利用度的研究[J]. 中国药科大学学报, 2018, 49(6): 682-688. DOI: 10.11665/j.issn.1000-5048.20180607
引用本文: 周生研, 张博文, 魏元锋, 钱帅, 张建军, 高缘. 共晶技术提高黄芩素溶出度及生物利用度的研究[J]. 中国药科大学学报, 2018, 49(6): 682-688. DOI: 10.11665/j.issn.1000-5048.20180607
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ZHOU Shengyan, ZHANG Bowen, WEI Yuanfeng, QIAN Shuai, ZHANG Jianjun, GAO Yuan. Enhanced dissolution and oral bioavailability of baicalein by cocrystallization[J]. Journal of China Pharmaceutical University, 2018, 49(6): 682-688. DOI: 10.11665/j.issn.1000-5048.20180607
Citation: ZHOU Shengyan, ZHANG Bowen, WEI Yuanfeng, QIAN Shuai, ZHANG Jianjun, GAO Yuan. Enhanced dissolution and oral bioavailability of baicalein by cocrystallization[J]. Journal of China Pharmaceutical University, 2018, 49(6): 682-688. DOI: 10.11665/j.issn.1000-5048.20180607
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共晶技术提高黄芩素溶出度及生物利用度的研究

  • 1.

    中国药科大学中药学院

  • 2.

    中国药科大学药学院

基金项目: 国家自然科学基金资助项目(No.81703712；No.81773675；No.81873012)；江苏省自然科学基金资助项目(No.BK20150703；No.BK20151438)；江苏省双创计划资助项目(2015)；江苏省高校品牌专业建设工程资助项目；中国药科大学“双一流”资助项目(No.CPU2018GY11,No.CPU2018GY27)

Enhanced dissolution and oral bioavailability of baicalein by cocrystallization

摘要

    摘要
  • 摘要: 采用混悬液结晶法制备1∶1物质的量比的黄芩素-咖啡因(BE-CA)共晶，以提高BE的溶出度及口服生物利用度。差示扫描热分析、X射线粉末衍射法、傅里叶红外光谱法等分析表明所制备的共晶为区别于BE及CA的一种长针状晶体新物质。溶出试验表明BE-CA共晶的溶出度均显著高于BE晶体及其与CA的晶体混合物。大鼠体内药代动力学研究表明，与BE相比，BE-CA共晶缩短BE及其活性代谢物黄芩苷(BI)的达峰时间(tmax)，并显著提高了BE及BI的峰浓度(cmax)及血药浓度-时间曲线下面积(AUC)，极大地提高了黄芩素口服生物利用度。
    Abstract: Baicalein(BE), a natural flavonoid mainly extracted from Radix Scutellaria, has comprehensive pharmacological actions such as anti-inflammation, anti-virus and anti-cancer activities. It belongs to BCS class II compound with relatively low oral bioavailability. The current study aims to improve its aqueous solubility and dissolution and hence to enhance its oral absorption by cocrystallization technique. Slurry crystallization method was employed to prepare baicalein cocrystal with co-former caffeine(CA), followed by physicochemical characterizations with DSC, XRPD and FTIR. Compared to BE and physical mixture of BE and CA, BE-CA cocrystal had a significantly higher dissolution of BE. In addition, in comparison to BE, this cocrystal achieved reduced time to peak(tmax)as well as significantly higher peak plasma concentrations(cmax)and area under the curve(AUCs)for both BE and its active metabolite baicalin(BI)in rats, suggesting enhanced the oral bioavailability of BE.
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  • 刊出日期:  2018-12-24

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