Preparation and characterization of Forms A and B of benazepril hydrochloride.
- Author:
Hong FANG
1
;
Xiu-rong HU
;
Jian-ming GU
;
Guan-xi CHEN
;
Jian-yue FENG
;
Gu-ping TANG
Author Information
- Publication Type:Journal Article
- MeSH: Benzazepines; chemistry; Crystallization; Drug Stability; Molecular Conformation
- From: Journal of Zhejiang University. Medical sciences 2012;41(6):639-646
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo prepare Form A and Form B of benazepril hydrochloride and to compare the differences in spectrums, thermodynamics and crystal structure between two polymorphic forms.
METHODSForm 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).
RESULTSPreparation 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 monoclone space group P2(1) with a=7.8655(4)Å, b= 11.7700(6)Å, c= 13.5560(7)Å, β= 102.9470(10)°, V=1223.07 (11)Å(3) and Z=2, while Form B belonged to orthorhombic space group P212121, with a=7.9353(8)Å, b=11.6654(11)Å, c=26.6453(16)Å, V=2466.5(4)Å(3) and Z=4. From the DSC and XRD results, Form B of benazepril hydrochloride could be transformed into Form A after heating treatment.
CONCLUSIONForm 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.