Abstract: OBJECTIVE To investigate the thermodynamics of curcumin-catechol co-crystals in which curcumin was used as the active pharmaceutical ingredient and catechol as the co-crystal conformer, in different solvents (methanol and ethyl acetate) and different temperature.METHODS Co-crystal was prepared by solid state grinding method, and characterized by X-ray diffraction. Solubility of curcumin-catechol co-crystals in different solvents (methanol and ethyl acetate solvent) and various temperatures were measured, followed by fitting the complexation model to calculate solubility products (K_sp) and complexation constants (K₁₁).RESULTS Based on the non-linear simulation, 1:1 complexation model was well fitted to the curcumincatechol co-crystal formation in methanol, while no complexation model was more suitable for that in ethyl acetate. The data K_sp increased while K₁₁ decreased with the reaction temperature.CONCLUSION The co-crystal is easily complexable in methanol when compared the co-crystal solubility products in two solvents. This thermodynamic study has provided a theoretical and applied foundation for the preparation and optimization of curcumin-catechol co-crystal.