热熔法制备曲普瑞林长效生物可降解微粒处方工艺的研究

Biodegradable Triptorelin Microsphere Prepared by Hot-Melt-Extrusion

关键词:  曲普瑞林长效生物可降解微粒  热熔法  处方工艺  质量控制

Key words:  sustained release biodegradable triptorelin microsphere  hot-melt extrusion  preparation technology  quality control

摘要:

目的 研究热熔法制备曲普瑞林长效生物可降解微粒的处方工艺，并对其质量进行考察。方法 首先进行单因素实验，对骨架材料PLGA的种类、PLGA与曲普瑞林重量比值、热熔挤出温度和时间、粉碎温度等参数进行筛选。在此基础上，对热熔挤出时间、热熔挤出温度、挤出后粉碎冷却温度3个因素进行正交试验，优化处方工艺，将制得的样品进行湿、热、光照影响因素试验，加速试验和长期试验考察。结果 热熔法制备的曲普瑞林微粒外观形态良好，且经加速试验考察，有关物质含量符合要求，微粒释放情况良好。结论 热熔法制备出的曲普瑞林质量稳定，该研究为制备出安全有效、质量可控的微粒提供理论与实践依据，适合进一步开发。

Abstract:

OBJECTIVE To study the preparation technology of sustained release biodegradable triptorelin microsphere prepared by hot-melt extrusion and its quality. METHODS First, conduct the single factor experiments to screening correlation parameters such as the kind of frame materials PLGA, PLGA and triptorelin weight ratio, hot melt extrusion temperature and time, grinding temperature and other parameters. On this basis, conduct orthogonal test about hot melt extrusion time, hot melt extrusion temperature, cooling temperature, to screen more accurate process conditions. The quality and stability of the newly designed microsphere were investigated by the influential factor test, accelerated test and long-term test. RESULTS The microspheres prepared by hot-melt extrusion had good morphology. And in the stability test, the content of related substances was in the required range and the accumulative dissolution was good. CONCLUSION The quality of sustained release biodegradable triptorelin microsphere prepared by hot-melt extrusion is stable and suitable for further development. Through these studies, provided a theoretical and practical basis for the safe and effective quality control on microspheres preparation.