Study of Complex Formation of Carbamazepine with Thiourea

Abstract

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.

What Has Carbamazepine Taught Crystal Engineers?

“…The number of crystal structures reported in the Cambridge Structural Database (CSD) that contain CBZ has increased significantly over the last 20 years (Figure ), and this trend illustrates the diversity and complexity of solid forms often found for drug compounds (Figure ). The CBZ solid form space includes polymorphs, cocrystals (including ionic cocrystals , and drug–drug cocrystals), ,− hydrates, a dihydrate, solvates, − and salts . CBZ has also been studied in inclusion complexes, , and in coamorphous systems …”