Designing of stable Co-crystals of clotrimazole using suitable coformers

The present study involves the preparation of co-crystal forms of clotrimazole with co-formers namely nicotinic acid and naringenin. Clotrimazole is a BCS class II drug withlow solubility and high permeability. Hence by preparing the co-crystal, an attempt has been made to improve its solubility. Based on thehydrogen bond formation between the API and co-former, two co-formers were selected: nicotinic acid and naringenin. The co-crystals of clotrimazole with nicotinic acid and naringenin were prepared in the molar ratios of 1:1, 1:2, and 2:1 using dry grinding and solvent evaporation. PXRD, DSC and FTIR confirmed the formation of co-crystals. The solubility of co-crystals of clotrimazole with nicotinic acid was increased 2.07 folds for the ratios 1:2 prepared by solvent evaporation method compared to pure clotrimazole. The saturation solubility was also increased for the co-crystals of clotrimazole with naringenin by 2 folds for the ratio 2:1 prepared by solvent evaporation method compared to pure clotrimazole.