制备奥拉帕利的6种晶型,研究其相对稳定性,采用X-射线粉末衍射分析、热分析、衰减全反射傅里叶红外光谱与拉曼光谱等多种分析检测技术对奥拉帕利6种晶型进行了固相表征,并通过高温转晶实验和溶剂介导实验研究晶型间的相对稳定性.奥拉帕利6种晶型中1种为水合物晶型H,2种为无水晶型A和L,3种为异质同晶溶剂化物,6种晶型的红外表征数据存在明显差异,可以用于6种晶型的鉴别及生产过程中的晶型控制.X-射线粉末衍射法、差示扫描量热法和拉曼光谱法在晶型A、H与L这3种晶型间存在较为明显的差异,可以用于这3种晶型的鉴别及生产过程中的晶型控制.无溶剂晶型间的稳定性关系为晶型A>晶型L,晶型A为热力学稳定晶型.
Six crystal forms of olaparib were prepared and their relative stability was studied.First of all,the forms were characterized by X-ray powder diffraction,thermal analysis,attenuated total refraction in-frared spectroscopy and Raman spectroscopy.Then,their relative stability was determined through high-temperature phase transformation and solvent-mediated transformation.Among these Six crystal forms,Form H is a hydrate,Form A and L are anhydrous,and the other three crystals are heteromorphic sol-vates.Also,there are obvious differences in the infrared spectroscopy data between the six solid forms,which can be used for the identification or polymorph control in the production process.There exist obvi-ous differences in X-ray powder diffraction,thermal analysis or Raman spectorscopy in A,H and L.Fur-thermore,Form A,L and H can also be identified and controlled by X-ray powder diffraction,thermal a-nalysis or Raman spectroscopy.In addition,the stability relationship is Form A>Form L for solvent-free Forms,that is to say,Form A is the most thermodynamic stable form.