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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。
Objective To prepare isosorbide mononitrate time-pulsed controlled release tablets (ISMN-5-PRT) and investigate the factors influencing drug release in vitro and pharmacokinetics in dogs. Methods ISMN-5-PRT was prepared by pressure-coating technique. The influence factors and mechanism of drug release were investigated. The pharmacokinetics and bioavailability of the drug were also studied. Results Hardness, the amount of coating, dissolution medium viscosity significantly affect the time lag. In addition to the drug through the proliferation of a small part of the release, mainly through the dissolution of the coating, rupture and release. In vitro release of ISMN-5-PRT in about 3h, release of more than 80% within 4h; Tmax of dogs were 5.3 ± 0.4,1.4 ± 0.5h and Camx were 288 ± 47,302 ± 69ng · ml-1, the relative bioavailability was 111.5% ± 8.6%. Conclusion ISMN-5-PRT has the characteristics of pulse release both in vitro and in vivo.