奥希替尼-苹果酸-丙酮合物共晶的合成、晶体结构及性质研究

Synthsis,Crystal Structure and Properties of Osimertinib-Malic Acid-Acetone Co-Crystal

以奥希替尼、苹果酸、丙酮为起始原料,合成了奥希替尼-苹果酸-丙酮合物共晶。通过X-射线单晶衍射、差热分析和拉曼光谱等手段进行了表征;采用Hirshfeld表面分析法对晶体结构中分子间相互作用进行了分析,其二维指纹图显示:H…H占整个Hirshfeld表面作用的51.8%;O…H(24%)、C…H(16.8%)、N…H(3.8%)作用力明显强于C…C(2.3%)、C…O(0.4%)、C…N(0.8%)的作用力;对共晶在不同条件下稳定性和溶解度进行了研究,结果显示,共晶稳定性优于市售甲磺酸奥希替尼,溶解度是市售甲磺酸奥希替尼的2倍,具有巨大的药用潜力。

Osimertinib-malic acid-acetone co-crystal was synthesized successfully using Osimertinib,malic and acid-acetone as the starting materials.The structure of co-crystals was characterized by single crystal X-ray diffraction,Synchronous thermal analysis and Raman spectroscopy.Intermolecular interaction was analyzed using Hirshfeld surface method,its two-dimensional fingerprint plots shows:H…H interactions to form into the crystal accounts for 51.8% in the total hirshfeld surface interaction,O…H(24%),C…H(16.8%)and N…H(3.8%)were stronger than C…C(2.3%),C…O(0.4%),C…N(0.8%).The solubility and the solubility of the co-crystal were also assessed,The results showed that the stability of co-crystal was better than Osimertinib mesylate in the market and the solubilities of co-crystal in various pH solutions were increased to two times as compared with Osimertinib mesylate in the market,it has great medicinal potential.