介孔分子筛MCM-41对吲哚美辛溶出度及其在大鼠体内生物利用度的影响

发布时间：2018-01-16 09:11

本文关键词：介孔分子筛MCM-41对吲哚美辛溶出度及其在大鼠体内生物利用度的影响　出处：《中国医药工业杂志》2015年12期 　论文类型：期刊论文

【摘要】：采用正硅酸乙酯为硅源,十六烷基三甲基溴化铵为模板剂,在碱性条件下合成介孔分子筛MCM-41;再用浸渍法制备吲哚美辛(1)/MCM-41组装体。利用X-射线衍射、氮吸附脱附等温线、红外光谱、热重分析等方法表征所得的MCM-41和组装体。结果表明,1成功组装于MCM-41孔道内,平均载药量可达15.9%。与1原料药相比,组装体提高了1的体外溶出速率,它在水中30 min时溶出率大于75%,90 min时大于90%。对比了大鼠单次灌胃给予1混悬液和组装体后的体内药动学行为。采用HPLC法测定大鼠血浆中的1。结果表明,1混悬剂组与组装物组的药动学参数如下:c_(max)(2.85±0.41)和(4.39±0.31)mg/ml;t_(max)(4.50±0.55)和(3.00±1.27)h;AUC_(0→t)(24.83±4.60)和(54.98±4.43)mg·h·ml~(-1);MRT(7.43±0.21)和(12.49±0.37)h。相对于1混悬剂,1/MCM-41组装体的相对生物利用度为236.9%。
[Abstract]:Mesoporous molecular sieve MCM-41 was synthesized by using ethyl orthosilicate as silicon source and cetyltrimethylammonium bromide as template. The indomethacin 1 / MCM-41 assembly was prepared by impregnation method. The isotherms of nitrogen adsorption and desorption were obtained by X- ray diffraction and IR spectra. Thermogravimetric analysis (TGA) was used to characterize the MCM-41 and the assembler. The results showed that TGA 1 was successfully assembled in the MCM-41 pore and the average drug loading was 15. 9%, compared with 1 API. The in vitro dissolution rate of 1 was increased by the assembler, and the dissolution rate of 1 was more than 75% when it was in water for 30 min. At 90 min, the pharmacokinetic behavior of rats was compared after single gastric administration of 1 suspension and assembly. The plasma of rats was determined by HPLC method. The results showed that the pharmacokinetic behavior of the rats was higher than that of the control group. The results showed that the pharmacokinetic behavior of the rats was determined by HPLC method. 1 the pharmacokinetic parameters of the suspension group and the assembly group were as follows: 1. The pharmacokinetic parameters of the suspension group and the assembly group were as follows: 1. The pharmacokinetic parameters of the suspension group and the assembly group were as follows:. And 3.00 卤1.27 hs; AUC_(0. 鈫扐nd 54.98 卤4.43 (mg 路h 路ml ~ (-1)) and 54.98 卤4.43 (mg 路h 路ml ~ (-1)) respectively. MRT(7.43 卤0.21) and 12.49 卤0.37 h. the relative bioavailability of MCM-41 was 236.9% compared with 1 / 1 suspension.
【作者单位】：哈尔滨商业大学药学院;
【基金】：黑龙江省教育厅科学技术研究项目(12541198)
【分类号】：R965
【正文快照】： 吲哚美辛(indometacin,1)亲脂性较高、水溶性极差,因此口服给药后体内溶出缓慢而导致其口服生物利用度低,从而影响临床应用。为改善1生物利用度,国内外进行了大量研究,如纳米粒、微乳和固体分散技术等[1-3],但这些技术中使用的有机高分子材料和有机溶剂存在潜在的安全性问题。

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