Measurement of glass transition temperatures of freeze-concentrated solutes by differential scanning calorimetry.

Thermal analysis of aqueous solutions in which the solute does not crystallize immediately upon freezing was carried out to define the effects of experimental parameters on thermograms in the glass transition region. The intensity of enthalpy relaxations in the glass transition region is related to both the rate of cooling and the rate of heating through the glass transition region--slow cooling or slow heating increases the extent of structural relaxation in the glassy state and increases the intensity of the endotherm. Plots of the logarithm of heating rate versus 1/Tg' are linear, and activation enthalpies for structural relaxation are in the range of 210-350 kJ/mol. For polymeric solutes, both the activation enthalpies for structural relaxation and the heat capacity change accompanying the glass transition increase with increasing molecular weight of the solute. Molecular weight dependence of the observed midpoint of the glass transition agrees with the Fox-Flory relationship. Results are compared and contrasted with glass transitions in solid polymers and with the glass transition of hyperquenched water. Practical implications for characterization of formulations intended for freeze-drying are discussed.