醋酸乌利司他优势药用晶型研究∗

摘要

目的：研究新型紧急避孕药醋酸乌利司他的多晶型现象，寻找对临床有效的优势药用晶型。方法通过多种物理或化学方法制备醋酸乌利司他的5种不含溶剂晶型样品和6种溶剂合物晶型样品；采用粉末X射线衍射分析法( PXRD)、热重分析法( TG)、差示扫描量热法( DSC)、红外光谱法( IR)对上述11种晶型样品进行表征；通过多种影响因素实验对晶型样品的稳定性和转晶规律进行研究。结果醋酸乌利司他存在多晶型现象，采用多种不同检测方法均可对其晶型进行鉴别。制备的11种晶型样品中有5种为首次发现。结论通过醋酸乌利司他的多晶型现象系统研究，阐明其多种晶型样品的物质组成、制备方法、晶型稳定性、溶解性及晶型转变规律，为优势药用晶型选择提供了科学基础数据，为提高药品质量、保证临床疗效、制定晶型药物质量控制标准提供科学依据。%Objective To study polymorphism of the newest emergency contraceptive ulipristal acetate and find preponderant pharmaceutical polymorphs which are efficient in the clinical medication. Methods Five non-solvates forms and six solvates forms of ulipristal acetate were obtained through physical or chemical methods. These polymorphs were characterized by X-ray powder diffraction analysis (PXRD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC) and infrared absorption spectroscopy (IR). Furthermore, a variety of experiments on influence factors were used to research the stability and transformation laws of the eleven polymorphs. Results This article demonstrated that ulipristal acetate had polymorphism and the polymorphs could be identified by kinds of detection methods. Eleven crystal forms of ulipristal acetate were discovered and 5 of them were found for the first time. Conclusion This research elucidates composition of a variety of crystal material, preparation methods, stability, solubility and laws of crystal transformation and provides scientific basic data for choice of preponderant pharmaceutical polymorphs. At the same time, the information lays the foundation for increasing drug quality, ensuring clinical quality, and drafting quality control standard of polymorph drugs.