Novel Pharmaceutical Cocrystal Consisting of Chlorzoxazone and Nicotinamide: A New Promising Carrier for Solubility Augmentation.

Abstract

Chlorzoxazone (CHZ) is a centrally acting muscle relaxant used to treat muscle spasms. It is employed as a first-line medication for treating muscle spasms, offering both musculoskeletal relaxation and mild sedative effects. According to the biopharmaceutics classification system, it belongs to class II drug having poor solubility and high permeability. In order to improve the flow property, water solubility, and dissolution of CHZ, CHZ-nicotinamide (NA) cocrystal was prepared by liquid-assisted grinding cocrystallization (LAG CC) method using methanol as the choice of solvent. CHZ-NA cocrystal was characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry, and scanning electron microscopy (SEM). DSC scan showed a sharp endothermic peak shift, which is caused by the formation of a new crystal form with altered physical properties, which was further confirmed by PXRD. Also, a change in the surface morphology of LAG CC compared to CHZ was observed in SEM. The resultant CHZ-NA cocrystal displayed improved powder flow properties compared to the native form of CHZ. LAG CC demonstrated a 3.1- and 2.6-fold increase in saturated solubility and intrinsic dissolution rate, respectively, compared to CHZ alone. Furthermore, the in vitro dissolution study showed that the cumulative dissolution of CHZ in 2 h was about 53%. Whereas, dissolution of LAG CC reached 99% in 2 h, showing obvious dissolution improvement. Thus, CHZ-NA cocrystal could significantly improve the flow properties, solubility and dissolution of CHZ.