Study of Complex Formation of Carbamazepine with Thiourea

• Published in: Chemical & pharmaceutical bulletin Vol. 62; no. 11; pp. 1125 - 1130
• Main Authors: Inoue, Yutaka, Sato, Sayuri, Yamamoto, Chisa, Yamasaki, Mikio, Kanamoto, Ikuo
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.11.2014; Japan Science and Technology Agency
• Subjects: Analgesics, Non-Narcotic - chemistry; carbamazepine; Carbamazepine - chemistry; complex; Crystallography, X-Ray; hydrogen bond; Hydrogen Bonding; Models, Molecular; Solubility; Spectroscopy, Fourier Transform Infrared; thiourea; Thiourea - chemistry; X-ray crystallography
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c14-00340

The aim of this study, we evaluated a complex between thiourea (TU) and carbamazepine (CBZ) of a poorly soluble drug by using powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, X-ray crystallography and the solubility test. PXRD of TU/CBZ=2/1, 1/1, and 1/2 prepared by solvent evaporation (EVP) revealed characteristic diffraction peaks at 2θ=6.7°, 8.8°, 13.5°, and 20.4°, therefore molecular interaction between TU and CBZ presumably occurred. Results of the FT-IR spectroscopy, asymmetric and symmetric NH stretching vibration of TU were shifted to high region by TU/CBZ=2/1, 1/1, and 1/2 EVP. TU/CBZ=2/1 and 1/1 EVP had absorption derived from TU. It was considered that complex were formed by TU/CBZ=1/2. X-Ray crystallography of TU and CBZ revealed a crystal structure with one TU molecule arranged near two CBZ molecules. Molecules of the same type overlap in this layer. When doing a solubility test by using CBZ and samples of EVP, physical mixture and crystals in TU/CBZ=1/2 to confirm the solubility in water of TU/CBZ complex, there is no difference with the CBZ. It considered that the structure of a complex differs from the tunnel structure of inclusion complexes that has been previously reported contribute to result it.