Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier
Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier
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DOI：
10.1016/j.ijpharm.2011.12.051
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发表时间：
2012-03-15
影响因子：
5.8
通讯作者：
Choi, Hoo-Kyun
中科院分区：
文献类型：
--
作者：
Seo, Sang-Wan;Han, Hyo-Kyung;Choi, Hoo-Kyun
姜黄素在生理pH下的溶解度通过与Solutol（R）HS 15形成固体分散体（SD）而显著增加。由于姜黄素发生水解降解，因此在pH 1.2、6.8和7.4缓冲介质中进行化学稳定性研究。HS 15表现出比RH 40和30更好的上级稳定效果。通过差示扫描量热法和X射线衍射研究，其特征在于分散在聚合物基质中的姜黄素的物理状态。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水解。在pH6.8的缓冲液中，SD（1：10）可提高姜黄素的溶出度，1h内药物释放率约为90%。固体分散体制剂在大鼠体内的药代动力学研究表明，与纯姜黄素相比，药物的生物利用度显着提高。含有1：10比例的药物和Solutol（R）HS 15的SD导致约5倍高的AUC（0- 12 h）。SD制剂在3个月的研究期间物理稳定。(C)2011 Elsevier B. V.保留所有权利。
Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol (R) HS15. Since curcumin undergoes hydrolytic degradation, chemical stability study was conducted in pH 1.2, 6.8 and 7.4 buffer media. Solutol (R) HS15 exhibited superior stabilizing effect to Cremophor (R) RH40 and Kollidon (R) 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 1 h. 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 (R) HS15 resulted in approximately 5 fold higher AUC(0-12h). SD formulation was physically stable over the study period of 3 months. (C) 2011 Elsevier B.V. All rights reserved.