【作者】 潘英娇；

【导师】 滕利荣； 王贞佐；

【作者基本信息】 吉林大学 ， 微生物与生化药学， 2008， 硕士

【摘要】 本文以流化床包衣造粒的方法制备了氨茶碱缓释微丸并对制剂的药动学性质作了相关研究。通过差示扫描量热法结合X-射线粉末衍射法和傅立叶变换红外光谱法考察了药物与辅料的配伍兼容性;采用单因素摸索的方法确定了空白丸心的制备工艺并且对丸心的粉体动力学性质作了评价;同样单因素方法确定了氨茶碱缓释微丸的包衣处方和制备工艺,制得12h持续释放的缓释制剂,通过体外释放试验并对释放曲线进行曲线方程拟合,研究了微丸的缓释机理;以家兔为实验动物,对制备的缓释微丸进行了药动学研究。结果表明,流化床造粒包衣法制备的氨茶碱缓释微丸体外释放行为符合一级动力学方程;与市售氨茶碱片相比,自制缓释微丸的T_max显著延长,C_max明显降低,达到了良好的缓释效果;动物体内分数和体外释放度试验拟合较好,可以用体外试验取代体内试验作为质量监测的方法;药动学实验结果表明自制的缓释微丸生物利用度良好。更多还原

【Abstract】 Film coating technique carried on by a fluidized bed spray coater is always used for preparing sustained-release pellets, which is more simple technology, less equipment need, less costs and more output capacity. Besides, the apparent fluidity of products made by fluidized bed is well, and there is no dust and mass during production. In this dissertation, aminophylline which is used for treating asthma, has been made in to sustained-release pellets. And the study was aiming at validation in vivo, consisting of preparation methods for pellets, the sustained- release system of coated pellets, pharmacokinetics. Results showed: the sustained-release pellets had good appearance and the drug was released in vivo over 12h.The drug-excipient compatibility was studied between aminophylline and self-made blank pellets, using the pellets on market as the reference. Differential scanning calorimetry (DSC) was used as a screening technique besides with FT-IR spectroscopy and X-ray powder diffractometry. Aminophylline was found to be compatibility with self-made blank pellets but pellets on market. The studies of release seemed to sustain the result.UV spectrophotometry was developed for in vitro assay during the studies of release , and the plasma concentration in rabbits was monitored by using the HPLC ultraviolet method.Blank pellets were layered by exipients in liquid phase which was also used for drug carrying. The effects of process variables were investigated. Finally the content of the drug in the pellets is 36%.Ethyl Cellulose was used for pellets coating. The effects of process variables and formulation variables on coating pellets preparation were investigated. And The results showed: the coated pellets had a marked sustained release property. The description of release profiles suggested that among the different kinetics, the first-order became the most appropriate model to describe release kinetics.Using the aminophylline pills on market as the reference, the pharmacokinetics in rabbits of self-made sustained-release pellets were studied. The result indicated that Tmax was longer, whereas Cmax was lower than the pills on market. Furthermore, the results showed that the sustained release preparation had satisfactory sustained release effects and there was good correlation between absorption percent in vivo and accumulative release in vitro. And the aminophylline sustained release pellets show a good bioavailability.更多还原