酒石酸美托洛尔四种时间依赖型延迟释药片的制备

Preparation of four kinds of time-dependent delayed release system of metoprolol tartrate

目的比较四种酒石酸美托洛尔时间依赖型延迟释药片（time-dependent delayed release tablets,TDDT）体外释放性质,为时间依赖型经口给予延迟释药片的应用提供理论依据。方法四种时间依赖型延迟释药片片芯以羧甲基淀粉钠和Na Cl为基础,采用聚乙二醇骨架片增加膜溶解物质聚乙二醇,采用蜡质膨胀骨架片增加膨胀剂半合成脂肪酸酯,采用有机酸基质片增加膜溶解物质酒石酸。均以EudragitNE 30D作为片芯控释包衣。结果固定片芯中羧甲基淀粉钠和Na Cl的用量,TDDT和蜡质膨胀骨架TDDT突释效果较明显,聚乙二醇TDDT和有机酸TDDT突释效果不明显,但后三者释药时滞稳定且批内溶出相似因子较高。聚乙二醇TDDT批内溶出相似因子略低于蜡质膨胀骨架TDDT和有机酸TDDT。结论增加蜡质骨架膨胀基质药物可突释且批内释药相似;增加控释膜溶解成份聚乙二醇和有机酸,药物无明显突释,但批内释药相似。

Objective To research the main design features and release performances of four time-dependent delayed release tablets TDDT,which relies on the relative constancy release. Methods The metoprolol tartrate TDDT tablets core was including CMS-Na and NaCl. PEG1000,wax-matrix and tartaric acid were added to the core tablets to prepare the PEG-base-matrix TDDT（ PEG-TDDT）,wax-matrix TDDT（ WMTDDT）and organic acid-induced TDDT（ OA-TDDT）,respectively. Core tablets were all coated with Eudragit NE 30 D as the coating materials. Results Burst drug release was observed in TDDT and WM-TDDT and not in PEG-TDDT and OA-TDDT. Meanwhile,WM-TDDT,PEG-TDDT and OA-TDDT had higher f2 than TDDT. Conclusions Wax-matrix TDCS can produce a burst drug release. WM-TDDT,PEG-TDDT and OA-TDDT have a steady release; also have the properties of delayed release system.