High potential of cocrystals in drug delivery¹ and functional materials² draws attention to the problems of rational design of cocrystals with desired properties. These properties including stability and solubility are determined by the difference in lattice free energy of a cocrystal and its constituents . Sublimation is used as a green and effective cocrystallization method ^{3, 4}; however, the only reports of cocrystal sublimation thermodynamics consider the systems where only one component is volatile. ^{5, 6}

We introduce the term ‘congruent sublimation’ for equilibrium of the solid cocrystal with the molecular vapor of its components of the same ratio. In the transpiration experiment, the [caffeine + 3-hydroxybenzoic acid] cocrystal vapor was carried by slow stream of nitrogen through a tube furnace and condensed downstream. The sublimate was identified as pure cocrystal by DSC, PXRD and FTIR spectroscopy. Vapor pressures of both components were determined to be close to equal according to HPLC analysis. Sublimation thermodynamic functions were derived according to Clausius-Clapeyron equation and corrected to 298.15 K using experimental solid molar heat capacities and theoretical gas-phase heat capacities. From the experimental sublimation functions of the cocrystal and literature data for pure components, cocrystallization thermodynamic functions were determined. Alternatively, the cocrystallization enthalpy and Gibbs energy were derived from solubility data of the cocrystal and pure components in acetonitrile at five different temperatures between 293 and 313 K.

The equality of vapor pressures of caffeine and hydroxybenzoic acid confirms the congruent sublimation across the experimental temperature range. No gas-phase complexes were observed in the synchronous DSC/TG/MS experiment. The cocrystal formation process was found to be enthalpy-determined. The cocrystallization enthalpy and Gibbs energy values derived from the sublimation and solubility cycles were found to be within 2 kJ/mol, which supports the proposed sublimation mechanism.