The
solubility of pharmaceutical cocrystals in aqueous solution
is influenced by pH-dependent dissociation and salt formation which
complicates the design of cocrystal formation and purification processes.
To increase the efficiency of those processes, the aqueous solubility
of pharmaceutical cocrystals was predicted in this work using perturbed-chain
statistical associating fluid theory (PC-SAFT). Modeling results and
experimental data of pH-dependent solubilities were compared for the
weak base nicotinamide, the weak acid succinic acid, their 2:1 cocrystal,
as well as for all occurring salts at 298.15 and 310.15 K. It was
found that the pH-dependent acid–base equilibria of nicotinamide
and succinic acid directly influence the solubility of their cocrystal
and their salts. By accounting for the thermodynamic nonideality of
the components in the cocrystal system, PC-SAFT is able to predict
the solubility behavior of all above-mentioned components in good
agreement with the experimental data.