Cocrystal formations of the anticonvulsant drug carbamazepine (CBZ) with para-aminosalicylic acid (PASA, antituberculous drug) have been studied by varying the molar ratio values of CBZ and PASA (1:1 and 2:1) and using liquid-assisted grinding (LAG), slurrying and solution crystallization methods. Three novel cocrystal forms of CBZ and PASA have been synthesized: [CBZ+PASA] (1:1), [CBZ+PASA+H2O] (2:1:1) and [CBZ+PASA+MeOH] (2:1:1), and their crystal structures have been described. A conformation analysis of the CBZ molecule in polymorphic forms, cocrystals, and its solvates has been conducted. Calculations of intermolecular interaction energies using the PIXEL approach have been carried out for CBZ cocrystals with stoichiometry 1:1. The melting and desolvation processes of the [CBZ+PASA] (1:1), [CBZ+PASA+H2O] (2:1:1) and [CBZ+PASA+MeOH] (2:1:1) cocrystals have been studied. A temperature dependence of the CBZ (form III) saturation vapor pressure has been obtained, and sublimation thermodynamic functions have been calculated. Based on the molecular crystals sublimation thermodynamics database, the standard sublimation thermodynamic functions of PASA have been evaluated. The thermodynamic functions of cocrystal formation based on CBZ have been calculated and analyzed. The dissolution process of [CBZ+PASA] cocrystal (1:1) in water (pH 7.4) has been studied. CBZ cocrystallization with PASA has been shown to lead to a dramatic decrease of the CBZ rate of conversion from anhydrous to hydrate form, as a consequence, to solubility improvement by approximately 1.5 times.
