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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%。
Mesoporous molecular sieve MCM-41 was synthesized by using tetraethyl orthosilicate as a silicon source and cetyltrimethylammonium bromide as a template, and then indomethacin (1) / MCM-41 assembly. The resulting MCM-41 and assembly were characterized by X-ray diffraction, nitrogen adsorption-desorption isotherms, infrared spectroscopy, thermogravimetric analysis and the like. The results showed that 1 successfully assembled in the MCM-41 channel, the average drug load up to 15.9%. Compared with 1 API, the assembly increased the in vitro dissolution rate of 1, which was more than 75% at 30 min in water and more than 90% at 90 min. The in vivo pharmacokinetic behavior of rats after a single oral administration of a suspension and assembly was compared. Determination of 1 in rat plasma by HPLC method. The results showed that the pharmacokinetic parameters of 1 suspension group and the assembly group were as follows: c max (2.85 ± 0.41) and (4.39 ± 0.31) mg / ml; t max (4.50 ± 0.55) and (3.00 ± 1.27) h; AUC_ (0 → t) (24.83 ± 4.60) and (54.98 ± 4.43) mg · h · ml -1, MRT (7.43 ± 0.21) and (12.49 ± 0.37) h respectively. The relative bioavailability of 1 / MCM-41 assembly relative to 1 suspension was 236.9%.