摘要
目的制备单硝酸异山梨酯定时脉冲控释片(ISMN-5-PRT)并考察体外释药的影响因素和家犬体内药动学。方法采用压制包衣技术制备ISMN-5-PRT,考察体外影响因素、释药机理,并进行家犬体内药动学和生物利用度研究。结果硬度、包衣层用量、溶出介质粘度对时滞影响显著。药物除少部分通过扩散释放外,主要是通过包衣层的不断溶蚀、破裂后释放。体外ISMN-5-PRT在约3h后开始释药,4h内释药大于80%;家犬体内定时脉冲释放片和普通片的Tmax分别为5.3±0.4、1.4±0.5h,Camx分别为288±47、302±69ng·ml-1,相对生物利用度为111.5%±8.6%。结论ISMN-5-PRT在体内外均具有脉冲释药特征。
Aim To investigate the preparation of isosorbide-5-mononitrate pulsatile release tablets（ ISMN-5-PRT）, and study the factors of influence on its release in vitro, the mechanism of drug release and the pharmacokinetics in dogs in vivo . Methods The pulsatile tablets of isosorbide-5-mononitrate were prepared with the press - coated techniques. The effect of formulation, medium and techniques on pulsatile release of ISMN-5-PRT was investigated under release test. The pharmacokinetics and bioavailability study in six dog subjects were performed by GC-ECD method. Results The hardness, weight of the outer shell and the medium viscosity had notable effect on the lag time of ISMN-5-PRT. The mechanism was confirmed by an erosion experiment. In vitro ISMN-5-PRT began to release drugs at about 3h and ended at about 4h, for the pulsafile - release tablets and normal tablets in vivo , Tmax were 5.3 ± 0.4h and 1.4 ± 0.5h, respectively, C were 288 ＋ 47ng·ml^-1 and 302 ＋ 69ng·ml^-1. The comparative bioavaiability of ISMN-5-PRT over the normal tablets was 111.5 % ± 8.6%. Conclusions The pulsatile release effect of ISMN-5-PRT was significant both in vitro and in vivo .
出处
《解放军药学学报》
CAS
2005年第4期258-261,共4页
Pharmaceutical Journal of Chinese People's Liberation Army
基金
全军医药卫生科研基金"十五"重点规划课题资助项目
No.01Z004
关键词
单硝酸异山梨酯
定时脉冲控释片
释药机理
药物动力学
生物利用度
Isosorbide mononitrate
Pulsatile Release tablets
Drug release mechanism
Pharmacokinetics
Bioavailability
