Insights into the Solubility and Structural Features of Four Praziquantel Cocrystals

Cocrystal technology can effectively improve the solubility and other physicochemical properties of compounds. The structural features of cocrystals are the key factors that affect the physicochemical properties. The present study aimed to investigate the solubility of the cocrystals formed between praziquantel and carboxylic acid compounds and understand the structural features of the cocrystals by exploring the intermolecular weak interactions between the components through theoretical computations. Four cocrystals were obtained, and their solubilities were all improved. The structures of the cocrystals were solved for the first time to reveal the structural features. Topology analysis based on the quantum theory of atoms in molecules and electron density difference analysis revealed the existence of classical and nonclassical hydrogen bonds. Energy decomposition analysis based on the symmetry-adapted perturbation theory was further applied to classify and quantify the interaction energy to better understand the composition of the interactions between the components. Notably, the tendency of the endothermic peak values of the cocrystals obtained from thermal analysis was consistent with the tendency of the physical component of maximum classical Coulomb interactions in the energy decomposition analysis and opposite to the tendency of the molecular weight of these cocrystals. In the end, the most promising one of the four cocrystals was selected as a candidate drug after taking into account safety and the improvement of the physicochemical properties.