西洛他唑-对羟基苯甲酸共晶制备新工艺

A new process for preparing co-crystal of cilostazol and p-hydroxybenzoic acid

目的制备西洛他唑-对羟基苯甲酸共晶(物质的量之比1∶1)。方法采用混悬液结晶法,以西洛他唑和对羟基苯甲酸为原料,硝基甲烷或乙腈为溶剂,室温条件下快速搅拌1 h,抽滤,干燥,即得目标产物。结果与结论应用X-射线粉末衍射(XRPD)、热重分析(TGA)、差示扫描量热分析(DSC)、红外光谱分析(IR)、单晶X-射线衍射(SCXRD)对本实验合成的西洛他唑-对羟基苯甲酸共晶物进行了表征。

In recent years, drug co-crystal has already become a new technology and strategy to improve the physicochemical properties and bioavailability as well as other properties of the active ingredients, which in- dicates its great development potential and widely application future in the medical community. Cilostazol and p-hydroxybenzoic acid were used as raw materials, nitromethane or acetonitrile as solvent, the mixture was stirred rapidly at room temperature for 1 h, then the suspension was filtered and dried to produce cilosta- zol-p-hydroxybenzoic acid co-crystal（ molar ratio 1：1 ）. Compared with the reported methods, which usually take 5 d, even 8 d with complex processes, our method has evident advantages. Notebly, this approach can provide some reference value for the establishment of an efficient, economical, environmentally friendly method in the industrial production. The cilostazol-p-hydroxybenzoic acid co-crystal was characterized by X- ray powder diffraction （XRPD）, thermal gravimetric analysis （TGA）, differential scanning calorimetry （ DSC ）, infrared spectroscopy （ IR）, X-ray single crystal diffraction （ SCXRD ）.