A theoretical and spectroscopic study of carbamazepine polymorphs

Abstract

The drug carbamazepine has been modeled, using ab initio density functional theory calculations [B3LYP/6-31G(d)], both as a single molecule and as a dimer. The predicted geometry of the single molecule calculation is compared with the crystallographic data on each of the polymorphs (carbamazepine forms I and III). From the predicted geometry it is possible to calculate the IR and Raman spectra; these predictions compare favorably with the observed spectra of both polymorphs of carbamazepine for most of the bands. The spectral differences between the polymorphs are more striking in the IR than the Raman spectra, with strong IR bands at 1688 and 1396 cm −1 in form I shifting to 1678 and 1388 cm −1 in form III. Analysis of the potential energy distributions for the calculated normal modes reveals that the vibrations are localized across different ring systems of the carbamazepine structure. Most notably, the polymorph-sensitive modes in the IR spectra are localized to the pendant CONH 2 group; it is these modes that show the greatest disparity from the calculated spectra, and it is this group that is perturbed in the polymorph crystal structures. The calculated dimer structure is similar to that of the single molecule, but the polymorph-sensitive IR modes are significantly better predicted by the dimer calculation.

Carbamazepine polymorphs: Theoretical and experimental vibrational spectroscopy studies

“…All displacements and new positions of the bands connected with carboxamide group confirmed that the active part of carbamazepine molecule is engaged in hydrogen bonding, which forms a dimer structure. Our findings are close to what was reported by Strachan et al [33]. In order to visualize the modes of carbamazepine molecule they described the percentage of PED for three groups: (A) referring to the motion of the aromatic rings, (B) as the motion of the central ring and (C) as the motion of NCONH 2 group.…”

“…The dihydrate was obtained by recrystallization from a wet ethanol solution [3,15]. The verification of carbamazepine crystals was based on the comparison of IR spectra obtained in this work and described in literature by other authors [3,13,15,33]. The spectral agreement of each polymorphic form is discussed in the text below.…”

“…Strachan et al [33] used computational methods for modeling of single molecule and dimer of carbamazepine by DFT theory calculations. The predicted geometry of the single molecule was compared with the crystallographic data of I and III polymorphic form of carbamazepine.…”

Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases

“…It can be related to the size of particles and their tendency to form agglomerates (Fig. 3), which can be high enough for Mie scattering (30,31). The increasing absorbance with the increasing terahertz frequency was described for lactose of various particle sizes as well as for amorphous indomethacin.…”

Simultaneous quantitative analysis of mebendazole polymorphs A–C in powder mixtures by DRIFTS spectroscopy and ANN modeling

“…It should be noted that in large molecules like mebendazole the normal vibrational modes are highly complicated, consisting of the concerted motion of many different atoms. Therefore, following Strachan et al [34], band assignments are proposed on the basis of percent PED and refer to portions of the molecule (benzimidazole, BZIMD, and benzoyl, Bz, rings, and methyl-carbamate, mCBM, moiety).…”