X-ray diffraction, vibrational and thermal study of dibenzazepinodione, a pharmacopeial impurity of oxcarbazepine

The antiepileptic drug oxcarbazepine (OXC) was crystallized from various organic solvents, and mixtures of OXC crystals and red-orange particles were obtained. In view of the pharmaceutical relevance of OXC, this study focuses on the isolation and characterization of these red-orange crystals by structural [single crystal (SCXRD), powder X-ray diffraction (PXRD) and Hirshfeld surface analysis], vibrational [Fourier transform infrared (FT-IR), Fourier transform Raman (FT-Raman) and Density functional theory (DFT) calculations], and thermal methods of analysis [simultaneous thermogravimetry-differential thermal analysis (TG-DTA) and hot stage microscopy (HSM)]. According to SCXRD, the red-orange crystals corresponded to a recently codified impurity of OXC, referred as dibenzazepinodione (DBZ) or impurity D in the United States and European Pharmacopoeias respectively, which crystallized in the orthorhombic Pccn space group with a half-molecule in the asymmetric unit. Hirshfeld surface analysis revealed that weak intermolecular contacts played an important role in the stabilization of DBZ packing. DBZ was also characterized through its mid-infrared and Raman spectra and its vibrational bands were assigned based on DFT calculations with the hybrid B3LYP functional, coupled with the 6-311++g (d,p) basis set. The TG-DTA and HSM results shed light on the behaviour upon heating of DBZ, revealing that this impurity is an unsolvated solid with high thermal-oxidative stability, which sublimed, melted locally and decomposed above 320 °C. The obtained results demonstrated that slow crystallization of OXC from solvents such as ethanol and dimethylsulfoxide, at 20-25 °C, in the presence or absence of ambient light afforded DBZ. The X-ray pattern based on the SCXRD data for DBZ is presented as reliable reference for its identification.