摘要
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.
作者
王嫦鹤
郭欢迎
王荪璇
刘海静
WANG Chang-he;GUO Huan-ying;WANG Sun-xuan;LIU Hai-jing(Shaanxi Institute for Food and Drug Control,Xi’an 710065,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2020年第1期170-176,共7页
Chinese Journal of Pharmaceutical Analysis
基金
国家科技重大专项重大新药创制(2017Z09101001)
陕西省社会发展攻关项目(2016SF-058).
关键词
阿立哌唑
多晶型
粉末X-射线衍射
差示扫描量热
偏光显微镜
傅里叶变换红外光谱
溶解特性
aripiprazole
polymorph
powder X-ray diffraction
differential scanning calorimetry
polarizing microscope
Fourier transform infrared spectroscopy
solubility properties