Journal of Physical Chemistry B, Vol.119, No.14, 4873-4880, 2015
Correlation between Glass-Forming Ability and Fragility of Pharmaceutical Compounds
Fragility is a measure of the departure from non-Arrhenius behavior for supercooled liquids and glasses, and various simple methods are available for its quantification. However, the obtained values usually do not agree with each other. One of the purposes of this study was to compare the fragility values obtained by different methodologies. Thermodynamic fragility (F-T) is a simple concept that is evaluated from the heat capacity change at the glass transition temperature (T-g). Dynamic fragility is evaluated using three methodologies in this study: extrapolation of the configurational entropy (S-c) to the Kauzmann temperature (T-k) (FDc), ramp-rate dependence of T-g (F-DTg), and that of the fictive temperature (T-f) (F(DT)f). F-T and FDc of 19 pharmaceutical compounds were correlated, whereas F-DTg and F-DTg did not correlate with either of them. This result seems reasonable because both F-T and FDc are calculated from thermodynamic parameters in the quasi equilibrium state, but F-DTg and F-DTf are likely affected by kinetics as well Another goal of this study was to find the correlation between the glass forming ability (GFA) and fragility. F-DTg was shown to correlate with GFA, presumably because both were determined on the balance of thermodynamic and kinetic factors. This correlation suggests that fragile glass has low GFA. Furthermore, the relevance of fragility to isothermal crystallization is discussed. Compounds with small F-DTg and F-DTf tended to exhibit pressure controlled crystallization, for which better storage stability can be expected relative to temperature-controlled compounds. Fragility was shown to be a useful parameter practically as well as scientifically.