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采用 Solutol® HS15 作为载体制备姜黄素固体分散体及其药代动力学评价。

Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier.

机构信息

BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, Republic of Korea.

出版信息

Int J Pharm. 2012 Mar 15;424(1-2):18-25. doi: 10.1016/j.ijpharm.2011.12.051. Epub 2011 Dec 31.

Abstract

Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol® HS15. Since curcumin undergoes hydrolytic degradation, chemical stability study was conducted in pH 1.2, 6.8 and 7.4 buffer media. Solutol® HS15 exhibited superior stabilizing effect to Cremophor® RH40 and Kollidon® 30. The physical state of the dispersed curcumin in the polymer matrix was characterized by differential scanning calorimetry and X-ray diffraction studies. SD preparation transformed curcumin into amorphous form and facilitated micellar incorporation, thereby preventing hydrolysis in aqueous medium. In vitro drug release in pH 6.8 buffer revealed that SD (1:10) improved the dissolution of curcumin with approximately 90% release of the drug within 1h. Pharmacokinetic study of the solid dispersion formulation in rat showed that bioavailability of the drug was significantly improved as compared to pure curcumin. SD containing 1:10 ratio of drug and Solutol® HS15 resulted in approximately 5 fold higher AUC(0-12h). SD formulation was physically stable over the study period of 3 months.

摘要

姜黄素在生理 pH 下的溶解度通过与 Solutol® HS15 形成固体分散体(SD)而显著提高。由于姜黄素会发生水解降解,因此在 pH 值为 1.2、6.8 和 7.4 的缓冲介质中进行了化学稳定性研究。Solutol® HS15 对 Cremophor® RH40 和 Kollidon® 30 表现出更好的稳定效果。通过差示扫描量热法和 X 射线衍射研究对聚合物基质中分散的姜黄素的物理状态进行了表征。SD 制剂将姜黄素转化为无定形形式,并促进胶束掺入,从而防止在水介质中发生水解。在 pH 值为 6.8 的缓冲液中的体外药物释放表明,SD(1:10)提高了姜黄素的溶解度,在 1 小时内约有 90%的药物释放。与纯姜黄素相比,SD 制剂在大鼠中的药代动力学研究表明,药物的生物利用度显著提高。含有 1:10 比例的药物和 Solutol® HS15 的 SD 制剂的 AUC(0-12h)约提高了 5 倍。在 3 个月的研究期间,SD 制剂在物理上是稳定的。

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