New Publication “Shortcut Method for the Prediction of the Cocrystal Solubility Line”

Peerapon Rapeenun, Juergen Rarey, and Adrian E. Flood
Cryst. Growth Des. 2021, 21, 10, 5534–5543

Knowledge of the solubility of a cocrystal in terms of solvent, temperature, and the liquid-phase concentrations of the active pharmaceutical ingredient and coformer is necessary for the pharmaceutical industry to produce pharmaceuticals with improved physicochemical properties. Here, we propose a simple and convenient shortcut calculation to predict the solubility curve of cocrystals using simple thermodynamic equations, considering the liquid-phase activity coefficient of the two species in the cocrystal, which does not require any fitting nor experimental solubility data of the cocrystal. Ibuprofen–nicotinamide and carbamazepine–nicotinamide cocrystals in ethanol were used to study the effect of temperature variation, while indomethacin–saccharin and carbamazepine–nicotinamide cocrystals were used to study the effect of solvents. Our prediction shows good results in both scenarios, which were supported by the absolute average deviation and the percent absolute relative deviation (% ARD) from the experimental data. Carbamazepine–nicotinamide in ethanol shows the best outcome with the lowest % ARD (9.0, 24.6, and 8.6% at 288.15, 298.15, and 308.15 K, respectively). Furthermore, we also illustrate the importance of the activity coefficient and any phase transition of the pure species in the calculation to achieve the most accurate result.

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