Fabrication of ceritinib cocrystals with improved solubility: Preparation, solid-state characterization, solubility studies, and molecular docking studies

Abstract

In the current research work, a new co-crystal of ceritinib with nicotinamide and quercetin hydrate was prepared with increased solubility. Ceritinib belongs to BCS class IV drug which having poor permeability and low aqueous solubility that leads to poor oral bioavailability. Thus, an endeavor has been made by the co-crystal technique to increase its solubility. Pharmaceutical co-crystals are also called multi-component crystals having a definite stoichiometric ratio of active pharmaceutical ingredients (APIs) and coformers and they are joined by noncovalent interactions such as hydrogen bonds, π–π packing, and Vander Waals forces. In current research work based on hydrogen bond formation the coformer selected were Nicotinamide and Quercetin Hydrate. The three ratios (1: 1, 1: 2 and 2: 1) of cocrystals of ceritinib with nicotinamide were prepared by the dry grinding method. The confirmation of formation of cocrystals was confirmed y powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier transform (FT) IR. Based on the saturation solubility studies, it obvious that the solubility of ceritinib with Nicotinamide was on the higher side as compare to Quercetin hydrate cocrystals and pure ceritinib The increase in solubility of cocrystals with Nicotinamide in ratios (1: 1, 1: 2 and 2: 1) increased by (119, 155.3, 83.1) fold as compared to Pure Ceritinib.