Preparation and Solid-State Characterization of Three Novel Multicomponent Solid Forms of Oxcarbazepine: Improvement in Solubility through Saccharin Cocrystal

Oxcarbazepine (OXCBZ) is an antiepileptic drug with low aqueous solubility, and its dissolution is the rate limiting step for absorption. The present work investigates three muticomponent solid forms of OXCBZ with water-soluble coformers with an aim to enhance its solubility and in vivo performance. The experiments based on the solution method yielded two cocrystals, with succinic acid (1) and saccharin (2) and a solvate with acetic acid (3). Compound 1 was identified by single crystal X-ray diffraction (XRD) as a solvated cocrystal involving eight molecules of OXCBZ, four molecules of succinic acid, and four molecules of chloroform in the unit cell. The structural changes upon desolvation of cocrystal 1 have also been examined. Single crystals of compounds 2 and 3 could not be obtained in a size suitable for single crystal X-ray analysis and thus was studied by differential scanning calorimetry, thermogravimetric analysis, hot stage microscopy, powder XRD, Fourier-transform infrared spectroscopy, and solid-state nuclear magnetic resonance spectroscopy. Furthermore, the powder dissolution of compounds 1 (desolvated form), 2, 3, and OXCBZ was performed in an acidic aqueous medium and analyzed by high performance liquid chromatography. Their physical stability was also assessed. The cocrystal with saccharin showed a significant improvement in the solubility of OXCBZ in aqueous conditions and exhibited a lower ED50 value as compared to pure OXCBZ.