Yes / Polymorphism in active pharmaceutical ingredients (APIs) can be regarded as critical for the potential that crystal form can have on the quality, efficacy and safety of the final drug product. The current contribution aims to characterize thermodynamic interrelationship of a dimorphic co-crystal, FI and FII, involving carbamazepine (CBZ) and saccharin (SAC) molecules. Supramolecular synthesis of CBZ-SAC FI and FII have been performed using thermo-kinetic methods and systematically characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), solubility and slurry measurements. According to Berger and Ramberger’s heat of fusion rule, FI (ΔHfus = 121.1 J/g, mp 172.5 °C) and FII (ΔHfus= 110.3 J/g, mp 164.7 °C) are monotropically related. The solubility and van’t Hoff plot results suggest that FI stable and FII metastable forms. This study reveals that CBZ-SAC co-crystal phases, FI or FII, could be stable to heat induced stresses, however, FII converts to FI during solution mediated transformation. / Authors would like to acknowledge UKIERI (TPR 26), EPSRC (EP/J003360/1, EP/L027011/1) for the support. Open Access funded by Engineering and Physical Sciences Research Council