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.