阿替洛尔缓释骨架片的研制.pdfVIP

摘 要 摘 要 阿替洛尔(Atenolol，ATN)为β肾上腺素受体阻滞剂，临床上主要用于治疗高血压、 心绞痛、心律失常和青光眼等。但该药普通制剂口服生物利用度低、个体差异大，易引 起血药浓度峰谷现象，不能起到平稳的降压效果。为了解决上述问题，因此本文以乙基 纤维素（EC ）和十六醇作为缓释材料，制备了阿替洛尔缓释骨架片。 本文对 ATN 在油相、水相中的平衡溶解度进行了测定，并建立了 UV 法来测定阿 替洛尔骨架片的释放度。该法操作简便，并满足该研究的各项分析要求。 在处方研究中，以缓释骨架片在 0~12 h 的释放度为考察指标，并考察了处方因素和 工艺因素对 ATN 缓释骨架片释放度的影响；并且在此基础上采用星点设计—效应面法 优化处方，筛选出最优处方，制成了阿替洛尔缓释骨架片。其最优处方为：EC (20 mpa.s) 为缓释阻滞剂，十六醇为辅助缓释辅料，加入一定量的硬脂酸镁以粉末直接压片法来制 备缓释片。按照优化处方制备的缓释片在 12 h 内释放度达到80 % 以上。 此外还考察了 ATN 缓释骨架片的释药机理，并采用零级模型、一级模型、Higuchi 模型和 Ritger-Peppas 模型等方程对制剂的体外释放曲线进行了模型拟合。结果表明， 释放曲线符合 Higuchi 方程，r = 0.991 ；同时也符合Ritger-Peppas 方程，r = 0.976 ，最终 判断缓释片的释药机理为非纯 Fick’s 扩散机制，即为药物扩散和骨架溶蚀协同作用的结 果，其中扩散机制起主要作用。 关键词 阿替洛尔 缓释骨架片 乙基纤维素 十六醇 星点设计-效应面优化法 I Abstract Abstract Atenolol (ATN) belongs to the β-receptor blocker, which has the main effect on hypertension, angina, arrhythmia and glaucoma and so on. However, the common dosage form of the drug has a low bioavailability and the individual difference is severe, which is easy to cause the blood concentration peak valley phenomenon. It cannot obtain a stable effect on the anti-hypertension. In order to deal with the problems mentioned above, EC and hexadecanol were taken as basic materials to prepare the ATN sustained release matrix tablets in this paper. In this study, a UV method was used for the determination of the equilibrium solubility of atenolol in oil and aqueous phase. According to the literature, UV spectrophoto- metry was adopted for the determination of ATN during the study of drug release rate. These methods were accurat