The Glass Transition of Co-Amorphous Pharmaceutical Molecular Glasses

The glass transition temperature (T_g) and related dynamics are investigated for binary miscible mixtures of a small molecule pharmaceutical and an excipient using differential scanning calorimetry. These mixtures are termed co-amorphous glasses, and such materials have been shown to have enhanced water solubility and bioavailability relative to the crystalline forms of active pharmaceutical ingredient. For the co-amorphous glasses studied, the composition-dependent T_g and the composition-dependent step change in the heat capacity (DeltaCp) both display negative deviations from expectations for an athermal mixture; both sets of data cannot be simultaneously described by current models of T_g based on configurational entropy, and implications are discussed. In addition, the cooling rate dependence of T_g and the fragility of each mixture is determined in an effort to clarify the relationship between fragility, ease of glass formation, and stability of the co-amorphous glass against crystallization.