Tg and Stability of Co-Amorphous Molecular Glasses

Co-amorphous molecular glasses are a relatively new class of materials with applications in pharmaceuticals and agrichemicals due to their higher solubility, dissolution rate, and bioavailability relative to, for example, the pure (crystalline) components. The glass transition temperature (T_g) and stability of binary co-amorphous molecular glasses are investigated as a function of composition. In such systems, a synergistic increase (or an antagonistic decrease) in the T_g over the value expected for the athermal mixture can occur due to strong (or weak) interactions between the two components. This synergy, or the lack thereof, is anticipated to impact stability against crystallization, dissolution kinetics, and bioavailability. Here we discuss our current work modeling T_g and heat capacity (Cp) for binary systems composed of active drugs and excipients, as well modeling the crystallization kinetics as a function of composition in the context of time-temperature-transformation (TTT) diagram. We find that the stability of the co-amorph is not directly related to fragility or to the ratio of T_g/T_m­. Rather, there is a competition between the driving force for crystallization, which is related to the temperature-dependent solubility of the two components, and the molecular mobility which is related to the glass transition temperature of the co-amorphous glass. In addition, we examine whether activity coefficient models can be used to describe both the solution thermodynamics and the glass transition in these mixtures.