LAUSR

Graphical abstract Figure. No caption available. ABSTRACT The aim of the present study was to evaluate the thermodynamic properties of in‐situ formation of cocrystal formulations by the melt‐mixing method. Specifically, the thermodynamic mixing behaviour of carbamazepine‐nicotinamide and ibuprofen‐nicotinamide cocrystals prepared with the aid of Soluplus® (SOL) were evaluated using thermodynamic lattice‐based solution theories. Thermodynamic miscibility of both cocrystals with SOL was predicted by calculating Gibb′s free energy based on the Flory‐Huggins (FH) interaction parameter (χ), while the activity coefficient of cocrystals estimated with the aid of solid–liquid equilibrium equation and FH lattice theory, showed good thermodynamic miscibility of the components at elevated temperatures used normally during melt‐mixing based processes. Complete phase transition diagrams constructed with the aid of DSC measurements and FH solution theory, suggested the existence of two transition zones: (1) a stable cocrystal zone, located at the right‐hand‐side of the spinodal phase separation curve, where stable cocrystals are prepared and (2) an unstable cocrystal zone, located at the left‐hand‐side of the spinodal curve up to liquidus, where the matrixforming polymer sets a kinetic barrier to recrystallization and hence, a barrier to the formation of cocrystals. The validity of the suggested thermodynamic phase transition zones was experimentally verified by ATR‐FTIR and hot‐stage polarized light microscopy.