Conformational and characterization of benidipine hydrochloride polymorphs: Spectroscopic and computational modeling investigations

Abstract Polymorphism has attracted increasing attentions due to its particular importance in the field of pharmaceutical industry, especially the studies on the conformations of different crystal structures. In this work, the relationship between crystalline forms and conformations of benidipine hydrochloride was systematically investigated by spectroscopic analysis with theoretical simulation. The structures of two polymorphs for benidipine hydrochloride were characterized on the basis of detailed study of Infrared spectroscopy, powder X-ray diffraction and differential scanning calorimetry. A method which combining IR, theoretical study and potential energy distribution was utilized to identify the monomeric conformers of benidipine hydrochloride in polymorphs. Simulations for the dimeric forms were also carried out by molecular electrostatic potential and natural bond orbital to improve the assignment of the bands in solid state and to analyze the intermolecular interactions. The results of calculated IR spectra showed highly accordance with experimental data, thus the conformers were demonstrated to be presented in the polymorphs appropriately. Furthermore, ab initio powder X-ray diffraction patterns were further simulated to estimate the attribution of conformers in polymorphic forms. The chemical and thermodynamic stability of two polymorphs were evaluated by the frontier molecular orbitals analysis and differential scanning calorimetry analysis.