卡维地洛凝胶骨架缓释片的处方优选与表征

Formulation Optimization and Characterization of Carvedilol Hydrogel Matrix Sustained-release Tablets

目的优选12 h内体外缓慢释药的卡维地洛凝胶骨架缓释片的处方工艺并进行表征。方法以2种型号的HPMC为骨架材料,通过正交试验法,优选处方工艺并验证,考察制剂在4种介质中12 h内的体外释放度,利用X-射线衍射法和红外光谱法分析药物的存在状态。结果最佳处方为卡维地洛7.5%,单硬脂酸甘油酯30%,HPMC K4M+E50占片重25%,HPMC K4M∶E50的比例为2∶1,乳糖占15%,硬度为3.5 kg;制剂在pH 1.2的介质中释药最快,12 h内达到90%以上,体外释药稳定(RSD<1.5%,n=3),符合Higuchi动力学方程,属于骨架溶蚀型释药系统;药物在片中以部分晶体存在,原辅料之间没有新键生成。结论该制备工艺简单,重复性良好,在12 h内具有良好的体外缓释特征。

OBJECTIVE To investigate the formulation process and characterization of carvedilol hydrogel matrix sustained-release tablets for slow release in vitro in 12 h. METHODS Two models of HPMC was used as hydrophilic matrix to prepare Carvedilol sustained-release tablets and the optimal formulation was screened by orthogonal test and validated. The release rate in vitro were investigated in four mediums. The existing state of sulfadiazine was identified by X-ray diffraction and IR spectroscopy. RESULTS The results showed that the optimal prescription was as follows:carvedilol of 7.5%, glycerin monostearate of 30%, HPMC K4M+E50 of 25%, the ratio of HPMC K4M to E50 was 2:1, lactose of 15%, the hardness of 3 kg. The release rate in vitro was the fastest within 12 h in the hydrochloric acid solution of pH 1.2, reaching over 90%, and the drug release was stable(RSD<1.5%, n=3). It was in line with Higuchi equation, which belonged to matrix erosion drug delivery system. Some crystals of the drug existed in the tablet, and there were no bonds between the main drug and excipients. CONCLUTION The preparation technology is feasible and exhibits perfect sustained-release characteristics in vitro in 12 h.