阿立哌唑不同晶型的制备、表征及溶解特性研究

Study on the preparation,characterization and solubility properties of different crystal forms of aripiprazole

目的:系统地研究阿立哌唑多晶型现象。方法:采用冷却析晶法、快速去溶剂法和双溶媒析晶法等制备阿立哌唑结晶产物,应用粉末X-射线衍射(PXRD)、差示扫描量热(DSC)、偏光显微镜及傅里叶变换红外光谱等方法对不同晶型进行表征和归属,并通过溶出度实验比较不同晶型的溶解性差异。结果:本研究制备了阿立哌唑的5种结晶产物,通过与相关专利数据对比进行归属,分别为晶型α、晶型Ⅰ、晶型Ⅲ、晶型Ⅳ、新晶型。不同晶型溶解性差异较大,5种晶型在水中的累积溶出度从高到低依次为新晶型、晶型Ⅲ、晶型α、晶型Ⅰ、晶型Ⅳ,在0.1 mol·L^-1盐酸溶液中的累积溶出度从高到低依次为晶型Ⅰ、晶型α、新晶型、晶型Ⅲ、晶型Ⅳ。结论:该研究数据为阿立哌唑晶型的质量控制提供了科学依据;所制备的新晶型有较好的溶解性,具有良好的应用和开发前景。

Objective:To study systematically on polymorphism of aripiprazole.Methods:The recrystallization products of aripiprazole were prepared by cooling crystallization method,rapid solvent removal method and doublesolvent crystallization method,respectively.The different crystalline forms were characterized and attributed by powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC),polarizing microscope and Fourier transform infrared spectroscopy(FTIR).The solubility properties of different crystalline forms were compared by dissolution experiments.Results:In this study,five recrystallization products of aripiprazole were prepared and assigned by comparing with relevant patent data,as crystal formα,formⅠ,formⅢ,formⅣand new form respectively.The solubility of different crystalline forms was quite different.The cumulative dissolution rates of five crystal forms in water from high to low were as follows:new form,formⅢ,formα,formⅠ,formⅣ,and in 0.1 mol·L^-1 hydrochloric acid as follows:formⅠ,formα,new form,formⅢ,formⅣ.Conclusion:The data provide a scientific basis for the crystal quality control of aripiprazole.The new crystals have good solubility,with a good application and development prospects.