Investigation of solid-liquid phase diagrams of the sulfamethazine-salicylic acid co-crystal

The influence of temperature and solvent on the solid-liquid phase diagram of the 1:1 sulfamethazine-salicylic acid co-crystal has been investigated. Ternary phase diagrams of this co-crystal system have been constructed in three solvents: methanol, acetonitrile and a 7:3 (v/v) dimethylsulfoxide-methanol mixture, at three temperatures. The system exhibits congruent dissolution in acetonitrile and the co-crystal solubility has been determined by a gravimetric technique. The Gibbs energy of co-crystal formation from the respective solid components has been estimated from solubility data, together with the corresponding enthalpic and entropic component terms. The Gibbs energy of formation ranges from -5.7 to -7.7 kJ mol^-1, with the stability increasing with temperature. In methanol and the DMSO-methanol mixture, the co-crystal dissolves incongruently. It is shown that the solubility ratio of the pure components cannot be used to predict with confidence whether the co-crystal will dissolve congruently or incongruently. The size of the region where the co-crystal is the only stable solid phase is inversely related to the pure component solubility ratio of salicylic acid and sulfamethazine.