Objectives: Drug–drug cocrystallization represents a promising approach for the development of novel combination drugs with improved physicochemical and biopharmaceutical properties. The aim of the present research is to prepare novel drug-drug cocrystalline forms of antiepileptic drug carbamazepine (CBZ) with sulfacetamide (SCTM). Methods: The novel CBZ cocrystal methanol solvate and cocrystal hydrate were prepared via solvent evaporation technique and characterized by single crystal X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Results: Single-crystal X-ray diffraction and thermal analysis revealed that the multicomponent solids are isostructural, wherein the solvent molecule does not play a structure-forming role. To optimize the synthesis of [CBZ+SCTM+H2O] (1:1:0.7), the binary and ternary phase diagrams were constructed in acetonitrile at 25 °C. A thorough investigation of the cocrystal hydrate behavior in aqueous solution showed that the pH of the dissolution medium exerted a significant effect on the stability and solubility of [CBZ+SCTM+H2O] (1:1:0.7). According to the dissolution and diffusion experiments in a buffer solution pH 6.5, the cocrystal hydrate characterized an enhanced dissolution rate and flux of CBZ. Pharmacokinetic studies in rabbits showed that the novel cocrystal hydrate exhibited a comparable bioavailability to the parent CBZ. Conclusions: Overall, this work reports the preparation of a novel CBZ drug-drug cocrystal hydrate, which can be considered as an alternative CBZ solid form for oral usage, possessing additive pharmacological effect.
