阿立哌唑多晶型的制备及表征

Preparation and Characterization of Polymorphisms of Aripiprazole

本研究共制备了阿立哌唑的7种晶型,即药用晶型一水合物和晶型Ⅲ,以及与药用晶型有关的晶型Ⅰ、晶型Ⅱ、晶型Ⅳ、晶型Ⅴ和半乙醇化合物。阿立哌唑的晶体可通过单一溶剂或混合溶剂经重结晶或不同温度加热等方法制备。通过粉末X射线衍射(PXRD)、差示扫描量热(DSC)、热重分析(TGA)和偏光显微镜等方法对不同晶型进行表征。本研究开发了3种新的晶型制备方法。试验表明,将一水合物和半乙醇化合物加热后会转变为晶型Ⅲ,而当在不同温度下直接加热晶型Ⅲ、晶型Ⅳ和晶型Ⅴ时,则会转变为晶型Ⅰ,且加热转晶过程并未引起有关物质增加。

Seven crystalline forms of aripiprazole were prepared in this study,namely two medicinal forms(the hydrate and form Ⅲ)and nonmedicinal forms(Ⅰ,Ⅱ,Ⅳ,Ⅴ and hemiethanolate).The polymorphisms of aripiprazole can be obtained by recrystallization from a single solvent or a mixed solvents or heating at different temperatures,and they were characterized by powder X-ray diffractometry(PXRD),differential scanning calorimetry(DSC),thermogravimetric analysis(TGA)and polarizing microscopy.In this paper,three new preparation methods were developed.The experimental results showed that the monohydrate and the hemiethanolate could be transformed into form Ⅲ after heating,while forms Ⅲ,Ⅳ and Ⅴ could be transformed into formⅠby heated directly at different temperatures.In addition,these transformations did not result in the formation of the related substances.