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%。
The mesoporous molecular sieve MCM-41 was synthesized with tetraethyl orthosilicate as silicon source and cetyl trimethylammonium bromide as templates under basic conditions. Then the assemblies of indometaein （1） and MCM-41 were prepared by immersion method. The characteristics of MCM-41 and the assemblies were investigated by X-Ray diffraction, N2 adsorption-desorption isotherm, FT-IR spectroscopy and thermogravimetric analyses. The results proved that I was loaded into the pore of MCM-41 successfully. The drug loading of the assemblies was 15.9%. Compared with the bulk drug, the in vitro dissolution rate of 1 from the assemblies was significantly increased. The dissolution of the assemblies at 30 min in water was above 75 %, and at 90 min was above 90 %. The pharmacokinetic behaviors of 1 in rats after single intragastric administration of 1 suspension or I/MCM-41 were compared. The drug concentrations in plasma were determined by HPLC. The main pharmacokinetic parameters of 1 suspension and 1/MCM-41 were as follows： Cmax （2.85±0.41） and （4.39±0.31）μg/ml; tmax （4.50±0.55） and （3.00±1.27）h; AUC0→t （24.83±4.60） and （54.98±4.43）μg.h.ml-1; MRT （7.43±0.21） and （12.49±0.37）h, respectively. Compared with 1 suspension, the relative bioavailability of the assemblies of 1/MCM-41 was 236.9 %.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2015年第12期1305-1310,共6页
Chinese Journal of Pharmaceuticals
基金
黑龙江省教育厅科学技术研究项目(12541198)
