Solid state and solubility study of a potential anticancer drug-drug molecular salt of diclofenac and metformin

• Both diclofenac and metformin have been shown to have anticancer activity. • The bioavailability of the drug–drug molecular salt was significantly higher than that of diclofenac and diclofenac sodium. • Hirshfeld surface analysis proved the formation of the intermolecular forces in the crystal structure. • The drug–drug molecular salt is a good form to improve the physicochemical properties of drugs. To improve the physicochemical properties of diclofenac (DFA) and exert its potential anti-tumor effect in combined pharmacotherapy of metformin (MET), a new drug-drug molecular salt of DFA and MET (DFA-MET) is formed and characterized. The single-crystal X-ray diffraction analysis shows that DFA-MET is a three-dimensional (3D) supramolecular structure constructed by different hydrogen-bonding interactions between DFA and MET with 1:1 stoichiometry by proton transfer reaction. In addition, Hirshfeld Surface analysis shows that both the hydrogen-bonding interactions and the Vander Waals maintain the 3D supramolecular structure of DFA-MET together. Compared with pure DFA and pure diclofenac sodium (NaDFA), the dissolving behavior and permeability of DFA-MET by forming drug-drug molecular salt in physiological pH environments are enhanced remarkably.