单硝酸异山梨酯定时脉冲控释片地研究.pdfVIP

单硝酸异山梨酯定时脉冲控释片的研究 1 2 孙学惠 郭涛 宋洪涛 隋因 沈阳军区总医院药剂科 辽宁 沈阳 110016 摘要 目的 制备单硝酸异山梨酯定时脉冲控释片 ISMN-5-PRT 并考察体内外释药特征 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 亲疏水性物质比 溶出介质黏度对时滞影响显著 药物除少部分通过扩散释放外 主要是通过药片衣层的不断溶蚀 破裂后释放 在体外 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 h 和1.4 0.5h Cmax 分别为288 47 ng·mL-1 和302 69 ng·mL-1 相对生物利用度为111.5 8.6 结论 ISMN-5-PRT 在体内外均具有显 著的脉冲释药特征 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 Studies on isosorbide mononitrate Pulsatile Release tablets Sun Xue-hui, Guo Tao, Song Hong-tao, Sui Yin (Department of Pharmacy, the General of Shenyang Military Region, Shenyang,China 110016) Abstract Aim To investigate the preparation ofisosorbide mononitrate pulsatile release tablets(ISMN-5-PRT),and study the influence factors on the release of it in vitro ,the mechanism of drug release and the pharmacokinetics. Methods The pulsatile tablets ofIsosorbide- 5- mononitrate was prepared with the press-coated techniques. The effects of formulation , medium and technics onpulsatile release of ISMN-5-PRT were investigated under release rate test.The pharmacokinetics and bioavailability study in six dogs subjects were performed by GC-ECD method. Results Hardness, the ratio of Hydrophilic and hydrophobic materials and viscosity had notable effects on the lag time of ISMN-5-PRT.The mechanism was assured by an erosion experiment.In vitro ISMN-5-PRT began to release the drug at about 3 hand ended at about 4 h; for the pulsatile-release tablets and normal tablets in vivo, the t were 5.3 0.4 h and 1.4 0.5h, respectively; max -1