米非司酮的无溶剂新晶型

Finding of a new solvent-free polymorph of mifepristone

目的:研究避孕药物米非司酮的多晶型现象。方法:通过多种物理/化学方法对米非司酮进行多晶型筛选;采用粉末X射线衍射分析法、差示扫描量热法、热重分析法和红外光谱法对筛选得到的多晶型样品进行表征;评价多晶型样品在高温、高湿、光照条件下的稳定性;绘制多晶型在6种不同溶剂介质中的溶解曲线。结果:通过多晶型筛选获得米非司酮的一种新晶型。除红外图谱外,该无溶剂晶型样品与米非司酮原料药的粉末X射线衍射图谱、差示扫描量热图谱、热重分析图谱均存在明显差异。新晶型在高温、高湿、光照条件下稳定。在0.2%十二烷基硫酸钠溶液、0.5%十二烷基硫酸钠溶液中,米非司酮新晶型的溶解度大于原料药。结论:米非司酮存在多晶型现象,通过筛选获得一种无溶剂的新晶型,该晶型的溶解度比米非司酮原料药好。通过粉末X射线衍射法、差示扫描量热法、热重分析法可区分新发现的米非司酮无溶剂晶型与米非司酮原料药。

Objective： To investigate polymorphism of the contraceptive mifepristone. Methods： Kinds of physical or chemical methods were used to assess mifepristone polymorphs. These polymorphs were characterized by X-ray powder diffraction analysis （PXRD） , differential scanning calorimetry （DSC） , thermogravimetric analysis （TG） and infrared absorption spectroscopy （IR）. A variety of influence factors were assessed to determine the stability of the polymorphs. The solubility curves were drawn in 6 solvents. Results： A new crystal form of mifepristone was discovered, and it had significant differences from mifepristone in PXRD, DSC and TG. The new polymorph was stable under high temperature, high humidity and strong light. The new polymorph had higher solubility than mifepristone in 0.2% SDS and 0.5% SDS. Conclusion： The polymorphism of mifepristone has been demonstrated. The new solvent-free polymorph has better solubility than mifepristone and they can be identified by PXRD, DSC and TG.