三水合艾司奥美拉唑镁反应结晶过程晶型控制

Crystal form control of the reactive crystallization process of esomeprazole magnesium trihydrate

对三水合艾司奥美拉唑镁制备过程中晶型控制进行研究,同时对产物的粒度分布等性质进行了工艺优化实验。通过X射线粉末衍射表征产物晶型,借助于二维在线成像系统监测三水合艾司奥美拉唑镁反应结晶过程中的晶体形貌变化,运用马尔文激光粒度仪辅助监测晶体的粒度分布变化。考察了结晶温度、反应物的浓度等因素对三水合艾司奥美拉唑镁晶型与晶习的影响。结果表明,三水合艾司奥美拉唑镁结晶方式为球形结晶,结晶温度是影响晶型的关键因素,优化后的结晶温度为25℃。优化后的工艺可以制备晶型固定、粒度分布均匀、平均粒度大的三水合艾司奥美拉唑镁药物颗粒。

Herein,esomeprazole magnesium trihydrate was prepared and its crystal form was controlled.Moreover,the properties of the product,such as the particle size distribution,were optimized.X-ray powder diffraction was used to characterize the crystal shape of the product.A two-dimensional online imaging system was employed to monitor changes in the crystal morphology during the reactive crystallization of esomeprazole magnesium trihydrate.A Marvin laser particle size analyzer was used to monitor changes in the particle size distribution.The effects of the crystallization temperature,reactant concentration,on the crystal form and mophorology of esomeprazole trihydrate magnesium were investigated.Results show that the crystallization mode of esomeprazole magnesium trihydrate is spherical and the crystallization temperature is the key factor affecting the crystal shape.The optimized reaction temperature was 25℃.Using the optimized process,drug particles of esomeprazole magnesium trihydrate with a fixed crystal shape,uniform particle size distribution,and large average particle size can be synthesized.