硫酸庆大霉素胃内滞留漂浮型缓释片的研制

DEVELOPMENT OF GENTAMICIN SULFATE SUSTAINED-RELEASE TABLET REMAINING-FLOATING IN STOMACH

本文根据流体动力学平衡控释系统原理,应有亲水性高分子和脂肪醇为辅料,研制了硫酸庆大霉素胃内滞留漂浮型缓释片。实验表明,本品的体外溶出符合一级动力学过程(K_r=0.3992h^(-1)).其溶出度在一定范围内不受片剂密度的影响。人胃内同位素γ-闪烁照相结果表明,本品在胃内的滞留时间(4h以上)明显长于普通片剂(1～2h).临床初步试验表明,本品一日两次,每次4万单位给药对幽门弯曲菌相关性胃炎的疗效与普通片一日三次,每次4万单位给药的疗效相似。稳定性加速试验(温度37～40℃,相对湿度75%,贮存3个月)表明,本品的有效期可暂定为两年。

Gentamicin sulfate sustained- release tablet remaining- floating in stomach (G- HBS) was developed based on the hydrodynamically balanced system. The dissolution rate of G-HBS was determined by rotary basket method(100 r/min, 37± 0.5℃, 0.1 mol/L HCl). The release characteristics of G- HBS showed basically first order kinetics with the dissolution rate constant (K_r) of 0. 3992 h^(-1). The mean dissolution time (MDT) of G- HBS was 2.53 h^(-1). The density of G- HBS was found to have no significant influence on dissolution of G- BHS. The γ- scintiphoto technique was used to examine the gastric retention time of G- HBS and GCT (gentamicin sulfate conventional tablet). It was shown that the gastric retention time of all subjects taking G- HBS under fed and fasted conditions were all over 4 h, in contrast with GCT, only 1～ 2 h. The stability of G-HBS was investigated and a tentative two-year expiration date was established. Spectrophotometry for the determination of gentamicin was established. The effect of G - HBS on Campylobacter pyloridis- associated chronic gastritis was examined through clinical trials.