Solubility of carbamazepine, nicotinamide and carbamazepine–nicotinamide cocrystal in ethanol–water mixtures

• Solubility of carbamazepine, nicotinamide were determined in ethanol + water mixtures.
• Solubility of carbamazepine–nicotinamide cocrystal was evaluated in the mixed solvent.
• Solubility of a drug in solvent mixture is dependent on solute/solvent–solvent interactions.
• Solubility of cocrystal depends on the coformer concentration and its stability in the solution.

Solubility is an important physiochemical property of pharmaceutical compounds, and cocrystallization is one method used to improve the solubility of drugs. Carbamazepine is a drug from class II, according to the biopharmaceutical classification system, and it forms a cocrystal with nicotinamide. Carbamazepine cocrystallized with nicotinamide was synthesized using the solvent evaporation approach, and its characteristics were determined using differential scanning calorimetry and powder X-ray diffractometry. The solubility of various solid phases in ethanol + water mixtures was investigated at different temperatures using the shake-flask method, and the resulting precipitates were characterized. The solubility of carbamazepine was increased with the addition of ethanol up to a mass fraction of 0.8. Nevertheless, maximum solubility of NIC is observed in neat solvent (water). While the solubility of a cocrystal depends on the concentration of the coformer and its stability in the solution.

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