盐酸贝那普利多晶型的制备和表征

Preparation and characterization of Forms A and B of benazepril hydrochloride

目的:获得制备盐酸贝那普利两种晶型——A晶型和B晶型的制备工艺,研究不同晶型的盐酸贝那普利在红外光谱、热稳定性和晶体结构上的差异,探讨两种晶型的转晶条件及稳定性关系。方法:用傅里叶红外光谱(IR)、热重(TG)、差示扫描量热法(DSC)、X射线粉末衍射(PXRD)、X射线单晶衍射(SCXRD)等分析手段,对盐酸贝那普利A晶型和B晶型分别进行表征研究。结果:获得了A晶型和B晶型的制备工艺、晶体结构及晶体稳定性。晶体结构分析表明,A晶型属单斜晶系,空间群P21,晶胞参数a=7.8655(4),b=11.7700(6),c=13.5560(7),β=102.9470(10)°,晶胞体积V=1223.07(11)3,晶胞内分子数Z=2。B晶型属正交晶系,空间群P212121,晶胞参数a=7.9353(8),b=11.6654(11),c=26.6453(16),晶胞体积V=2466.5(4)3,晶胞内分子数Z=4。从DSC和XRD结果表明B晶型热处理后会转变成A晶型。结论:盐酸贝那普利A晶型和B晶型都是无水晶型,是分子构型不同产生的多晶型,A晶型的高温稳定性优于B晶型。

Objective： To prepare Form A and Form B of benazepril hydrochloride and to compare the differences in spectrums,thermodynamics and crystal structure between two polymorphic forms.Methods： Form A and Form B of benazepril hydrochloride were characterized by Fourier transform infrared spectroscopy（IR）,thermal gravimetric analysis（TG）,differential scanning calorimetry（DSC）,powder x-ray diffraction（PXRD） and single crystal x-ray diffraction（SCXRD）.Results： Preparation method,crystal structure and polymorphic stability of Form A and Form B of benazepril hydrochloride were obtained.Based on the analysis of crystal structure of both polymorphs,Form A belonged to monocline space group P21 with a=7.8655（4）,b= 11.7700（6）,c= 13.5560（7）,β= 102.9470（10）°,V=1223.07（11）3 and Z=2,while Form B belonged to orthorhombic space group P212121,with a=7.9353（8）,b=11.6654（11）,c=26.6453（16）,V=2466.5（4）3 and Z=4.From the DSC and XRD results,Form B of benazepril hydrochloride could be transformed into Form A after heating treatment.Conclusions： Form A and Form B of benazepril hydrochloride are both anhydrous and displayed different polymorphs due to different molecular configuration.Furthermore,Form A exhibits more stable than Form B at high temperatures.