阿哌沙班-烟酸一水合物共晶的制备、表征及性质研究

Preparation,characterization and properties of apixaban-nicotinic acid monohydrate co-crystal

目的制备阿哌沙班-烟酸一水合物共晶(物质的量之比1∶1∶1)。方法采用溶媒结晶法,以阿哌沙班和烟酸为原料、三氟乙醇-乙酸乙酯为结晶溶剂体系,室温条件下用含水0.5%(体积分数)的三氟乙醇搅拌3 h溶解澄清,之后加入乙酸乙酯析晶2 h,过滤,干燥,得到目标产物。结果与结论应用^(1)H-NMR分析、元素分析、含水量分析、X-射线粉末衍射(XRPD)、差示扫描量热分析(DSC)、热重分析(TGA)、红外光谱分析等对本试验合成的阿哌沙班-烟酸一水合物共晶物进行了表征。对共晶稳定性、溶解性和引湿性进行了研究,相较于阿哌沙班,共晶在不同pH介质中的溶解度提高了2~3倍,理化成药性良好。

Apixaban-nicotinic acid monohydrate co-crystal,which was composed of a molecule apixaban,a molecule nicotinic acid and a molecule water.Apixaban and nicotinic acid were respectively dissolved in trifluoroethanol containing 0.5% water at 25 ℃ and stirred 3 h.And then added ethyl acetate and stirred 2 h at same temperature to precipitate the co-crystal.The co-crystal was obtained through filtering and drying.The structure of co-crystal was characterized by ^(1)H-NMR,elements analysis,water content analysis,X-ray power diffraction(XRPD),differential scanning calorimetry(DSC),thermal gravimetric analysis(TGA) and infrared(IR) spectrum,respectively.The stability,solubility and hygroscopicity of the co-crystal were also assessed.The results showed that the solubility of co-crystal in various pH solution were increased to two to three times as compared with apixaban.The physical and chemical properties of co-crystal are very good.■。