沃替西汀盐晶体结构及理化性质

Crystal structure and physicochemical properties of vortioxetine salts

沃替西汀(VOT)是一种治疗重度抑郁症的抗抑郁药,由于其水溶性低,限制了其生物利用度和疗效,期望通过成盐方式来改善沃替西汀的水溶性。利用溶剂缓慢挥发法成功制备了2种沃替西汀盐〔沃替西汀-2-吡啶甲酸(2PA)盐(VOT-2PA)和沃替西汀-异烟酸(4PA)盐一水合物(VOT-4PA·H2O)〕,并通过单晶X衍射数据确定了它们的晶体结构。结果表明,VOT-2PA和VOT-4PA·H2O具有相似的N—H…O氢键基础框架。并对晶体结构进行了Hirshfeld表面计算,以便从微观结构深入了解弱作用力之间的差异。利用红外光谱、差式扫描量热法和粉末X射线衍射对2种沃替西汀盐进行了表征和分析。与沃替西汀原料药相比,2种新盐均表现出更好的热稳定性和溶解度。结果表明,VOT-2PA和VOT-4PA·H2O均具有改变VOT理化性质的能力。

Vortioxetine is an antidepressant for the treatment of major depressive disorder,low water solubility limits its bioavailability and efficacy. It is expected to improve the water solubility of vortioxetine by salt formation. Two vortioxetine salts [with 2-picolinic acid(2 PA)(VOT-2 PA) and isonicotinic acid(4 PA)(VOT-4 PA·H2 O)] were successfully prepared by slow solvent evaporation method. Their crystal structures were determined from single-crystal X-ray diffraction data. Structural analyses showed that VOT-2 PA and VOT-4 PA·H2 O had the similar N—H…O hydrogen bond base frame. The crystal structure was calculated by Hirshfeld surface method to understand the difference between the weak forces from the microstructure. The two vortioxetine salts were characterized and analyzed using infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Compared with vortioxetine, the two salts showed better thermal stability and solubility. It is found that both VOT-2 PA and VOT-4 PA·H2 O had the ability to change the physicochemical properties of VOT.