Probenecid and benzamide: DSC applied to the study of an “impossible” pharmaceutical system

The study of the binary system probenecid–benzamide is an excellent example of the power and the limits of thermal analysis applied to the investigations of compounds of pharmaceutical interest. The DSC curves obtained for the drug:coformer physical mixtures show a challenging pattern of endo/exothermal peaks heavily dependent on the system composition and the heating rate. Curves are so complicated that, at a first glance, their interpretation appears nearly impossible. We developed a thermodynamic model that addresses all the single processes which could take place during heating and should appear in the DSC curves if enough time was left to their occurrence and if they didn’t hidden reciprocally for kinetics reasons: melting of the metastable eutectic mixture formed by probenecid and benzamide (EU1) with composition xPRO = 0.2; crystallization of the cocrystal (CC) with composition xPRO = 0.5 and of the excess component with respect to the cocrystal composition; melting of the eutectic mixture formed by the cocrystal and benzamide (EU2) with composition xCC = 0.4; melting of the cocrystal. The model here proposed well agrees with the enthalpy values measured for the physical mixtures of different composition.