The glass transition temperature of co-amorphous molecular glasses with strong interactions

The glass transition temperature (T_g) of binary miscible mixtures of molecular glasses, termed co-amorphous materials, is often synergistically increased over the T_g of the two components. This synergy is thought to arise from the strong interactions between the two species, and it is particularly important for pharmaceutical co-amorphous formulations, where T_g and the molecular interactions between the components of the co-amorph are important for determining the shelf life of the drug, its stability against crystallization and phase separation, its dissolution kinetics, and its in-vivo precipitation. Current models that describe the compositional dependence of T_g, including the Gordon-Taylor, Braun-Kovacs, and Kwei equations, fail to predict the T_g increases observed in co-amorphous pharmaceutical systems with strong interactions. In this study, a robust thermodynamic framework is developed extending Gordon and Taylor’s configurational entropy approach using the excess entropy and models of the activity coefficient, in order to model T_g of several pharmaceutical co-amorphous molecular mixtures. The non-random two-liquid (NRTL) activity coefficient model well describes the synergistic increase in T_g in these systems.