Abstract
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 degrees C. The obtained results demonstrated that
slow crystallization of OXC from solvents such as ethanol and
dimethylsulfoxide, at 20-25 degrees 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. (C)
2019 Published by Elsevier B.V.
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