共载阿司匹林-埃索美拉唑镁肠溶微丸的研制与评价

在前期分别制备阿司匹林和埃索美拉唑镁肠溶微丸的基础上,本试验设计了共载阿司匹林-埃索美拉唑镁肠溶微丸。首先采用挤出-滚圆法制备含阿司匹林的丸芯,然后用流化床底喷包衣法,依次包隔离层Ⅰ、埃索美拉唑镁、隔离层Ⅱ和肠溶衣层,最终制得共载阿司匹林-埃索美拉唑镁的肠溶微丸。体外释放结果表明,该微丸中2种药物在0.1 mol/L盐酸中2 h内的累积释放率小于5%;随后在pH 6.8磷酸盐缓冲液中,15 min内阿司匹林和埃索美拉唑镁的累积释放率为(5.9±1.1)%和(78.5±1.4)%,60 min时为(77.4±3.3)%和(83.5±1.9)%。大鼠体内药动学结果表明,埃索美拉唑镁和阿司匹林的代谢产物水杨酸的tmax、AUC0→∞、cmax、MRT0→∞分别为(1.50±0.00)和(3.50±0.50)h、(15.73±2.50)和(1158.39±73.73)mg·L^-1·h、(2.89±0.09)和(75.13±2.14)mg/L、(8.30±1.30)和(11.68±0.60)h。本试验所得共载药微丸中埃索美拉唑镁在pH 6.8介质中能快速释药,阿司匹林则经一定时滞后再释放,有利于发挥两药协同作用,减轻阿司匹林长期应用对胃肠道的刺激性。

Preparation and Evaluation of Aspirin and Esomeprazole Magnesium Co-loaded Enteric-coated Pellets

On basis of our previous research of the enteric-coated pellets loaded with aspirin or esomeprazole magnesium,the co-loaded enteric-coated pellets were prepared in this paper.Firstly,the aspirin pellet cores were fabricated by extrusion-spheronization method,then the cores were sequentially coated with the isolation layer Ⅰ,esomeprazole magnesium layer,isolation layer Ⅱ and enteric layer by bottom spray-type fluid-bed coating process to obtain the final product,the aspirin and esomeprazole magnesium co-loaded enteric-coated pellets.The results of in vitro test showed that the cumulative releases of two drugs from the pellets were below 5%in 0.1 mol/L hydrochloric acid within two hours,while in pH 6.8 phosphate buffer,the cumulative releases of aspirin and esomeprazole magnesium were(5.9±1.1)%and(78.5±1.4)%for 15 min,(77.4±3.3)%and(83.5±1.9)%for 60 min,respectively.The pharmacokinetic test of the co-loaded enteric-coated pellets was carried out with rats as the models.The tmax,AUC0→∞,cmax and MRT0→∞in rats after gavage administration were(1.50±0.00)and(3.50±0.50)h,(15.73±2.50)and(1158.39±73.73)mg·L^-1·h,(2.89±0.09)and(75.13±2.14)mg/L,(8.30±1.30)and(11.679±0.60)h respectively.There results showed that esomeprazole magnesium could burst release in pH 6.8 medium,while aspirin could release after a certain time lag,which was conducive to play a synergistic effect and reduced the gastrointestinal irritation of aspirin in long-term application.