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

Author(s)

Faudone, Sonia N. ^[1] ; Paschoal, Alexandre R. ^[2] ; Carvalho Jr, Paulo S. ; Ellena, Javier ^[3] ; Martins, Felipe Terra ^{[3, 4]} ; Cuffini, Silvia L. ^{[1, 5]} ; Ayala, Alejandro P. ^[2] ; Sperandeo, Norma R. ^{[6, 7]}

Affiliation

^[1] CEPROCOR, Ctr Excelencia Prod & Proc Cordoba, Alvarez de Arenales 180, X5004AAP Cordoba, Cordoba - Argentina

^[2] Univ Fed Ceara, Dept Fis, Caixa Postal 6030, BR-60455900 Fortaleza, Ceara - Brazil

^[3] Carvalho Jr, Jr., Paulo S., Univ Sao Paulo, Inst Fis Sao Carlos, Caixa Postal 369, BR-13560970 Sao Carlos, SP - Brazil

^[4] Univ Fed Goias, Inst Quim, Campus Samambaia, CP 131, BR-74001970 Goiania, Go - Brazil

^[5] Univ Fed Sao Paulo, Inst Ciencia & Tecnol, Campus Sao Jose dos Campos, Rua Talim 330, BR-12231280 Villa Nair - Brazil

^[6] Univ Nacl Cordoba, Dept Ciencias Farmaceut, Fac Ciencias Quim, Ciudad Univ, X5000HUA Cordoba, Cordoba - Argentina

^[7] Univ Nacl Cordoba, Unidad Invest & Desarrollo Tecnol Farmaceut UNITE, Fac Ciencias Quim, CONICET, Ciudad Univ, X5000HUA Cordoba, Cordoba - Argentina

• Document type: Journal article
• Source: Journal of Molecular Structure; v. 1182, p. 204-212, APR 15 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 12/05616-7 - Solid-state characterization of anticonvulsant and antidepressant phamaceutical compounds: Design of new crystal forms.
• Grantee: Paulo de Sousa Carvalho Júnior
• Support Opportunities: Scholarships in Brazil - Doctorate