Effects of annealing on enthalpy relaxation in lyophilized disaccharide formulations: mathematical modeling of DSC curves.

The overall objective of these studies was to investigate, by experimental studies and theoretical analysis, the optimum annealing conditions to obtain maximum structural relaxation in lyophilized glasses of pharmaceutical significance. The model formulations used in this work were aspartame: sucrose and aspartame: trehalose (1:10 w/w) freeze-dried glasses. In this article, structural relaxation in amorphous systems was described in terms of the change in the fictive temperature (T(f)) and was measured using the enthalpy relaxation endotherm in a differential scanning calorimeter (DSC). The theoretical analysis was performed using the Tool-Narayanaswamy-Moynihan (TNM) model. The effect of different annealing conditions (temperature and time) on fictive temperature obtained from the theoretical analysis was calculated and compared with the experimental results. The model reproduced the experimental data very well for samples that were quench cooled from the liquid. However, the model fits were poor for lyophilized samples, indicating an inability to incorporate the complex thermal history of freeze-drying in the TNM model. The optimum aging conditions were determined from both DSC and approximated best-fit parameters of the TNM model, and it was found that annealing when done at a temperature about 15-25 degrees C below T(g) resulted in maximum structural relaxation.