羧甲基玉米朊阿司匹林肠溶微丸的制备及体外释放度考察

Preparation of Carboxymethyl Zein Aspirin Enteric-coated Pellets and Its Release Rate in vitro

目的:制备羧甲基玉米朊阿司匹林肠溶微丸,并考察其在大鼠体内的药动学特征。方法:以羧甲基玉米朊为肠溶材料,与阿司匹林按2∶1混合,加入乙醇作为黏合剂,采用挤压滚圆法制备羧甲基玉米朊阿司匹林肠溶微丸。以阿司匹林微丸作为参比制剂,考察受试制剂羧甲基玉米朊阿司匹林肠溶微丸灌胃给予15 mg/kg后在大鼠体内48 h内的药动学特征和4 h(前2 h在人工胃液中,后2 h在人工肠液中)内的体外释放度(n=5)。结果:所制羧甲基玉米朊阿司匹林肠溶微丸粒径为1 mm,规格为每丸3 mg。受试制剂与参比制剂的药动学特征均符合二室模型,主要药动学参数分别为t1/2β:(12.63±0.60)、(2.42±0.61)h,tmax:(11.07±1.10)、(3.41±0.84)h,cmax:(34.45±5.33)、(45.78±3.30)μg/ml,AUC0-∞:(613.52±41.14)、(550.69±34.44)μg·h/ml;与参比制剂比较,受试制剂的t1/2β、tmax、AUC0-∞均明显增加,cmax明显减小(P<0.05)。参比制剂2 h的累积释放度为87%,受试制剂2 h的累积释放度为1.7%、3 h的累积释放度达100%。结论:成功制得体外释放符合肠溶制剂要求的羧甲基玉米朊阿司匹林肠溶微丸。

OBJECTIVE：To prepare Carboxymethyl zein aspirin enteric-coated pellets,and to investigate pharmacokinetic characteristics of it in rats. METHODS：Carboxymethyl zein was used as enteric-coated material and mixed with aspirin with ratio of 2 ∶1 using ethanol as adhesive. Carboxymethyl zein aspirin enteric-coated pellets were prepared by extrusion spheronization method.Using Aspirin pellets as reference preparation,48 h pharmacokinetic characteristic and 4 h in vitro drug release of Carboxymethyl zein aspirin enteric-coated pellets as test preparation were investigated in rats after intragastric administration of test preparation 15mg/kg（n=5）. RESULTS：Prepared pellets was 1 mm in particle size and 3 mg/pellet in specification. The pharmacokinetics of both reference and test preparations were in line with two-compartment model. Main pharmacokinetic parameters of reference preparations vs. test preparations：t1/2β：（12.63±0.60）h vs.（2.42±0.61）h;tmax：（11.07±1.10）h vs.（3.41±0.84）h;cmax：（34.45±5.33）μg/ml vs.（45.78±3.30）μg/ml;AUC0-∞：（613.52±41.14）μg·h/ml vs.（550.69±34.44）μg·h/ml. Compared with reference preparation,t1/2 β,tmaxand AUC0- ∞of test preparation increased significantly,while cmaxdecreased greatly（P〈0.05）. 2 h accumulative release rate of reference and test preparation were 87% and 1.7%,and test preparation was released completely within 3 h. CONCLUSIONS：Prepared Carboxymethyl zein aspirin enteric-coated pellets which are up to the requirements of enteric-coated preparation are prepared successfully.