Journal of Physical Chemistry B, Vol.119, No.22, 6820-6827, 2015
Local Minimum in Fragility for Trehalose/Glycerol Mixtures: Implications for Biopharmaceutical Stabilization
Approximately a decade ago it was observed that adding a small amount (5 wt %) of glycerol to trehalose could substantially improve the stability of enzymes stored in these glasses even though the final glass transition temperature (T-g) was reduced by similar to 20 K. This finding inspired great interest in the fast dynamics of dehydrated trehalose/glycerol mixtures, leading to the observation that suppression of fast dynamics was optimal in the presence of similar to 5 wt % of glycerol. It was also recognized that the fast dynamics should, in theory, be related to the fragility of these glass formers, but experimental confirmation of this hypothesis has been lacking for trehalose/glycerol mixtures or any other mixtures of this nature In the present study a dynamic mechanical analyzer (DMA) was used to determine both the T-g and the kinetic fragility index (m) of trehalose/glycerol mixtures within the mass fraction range of 80-100 wt % of trehalose. It was found that the fragility index correlated with the mass fraction of trehalose in a nonmonotonic manner, with a local minimum between 87.5 and 95 wt % of trehalose, whereas the composition dependence of T-g was found to follow a Gordon-Taylor like relationship, with no local minimum. The composition of 5-12.5 wt % glycerol in trehalose thus yielded a matrix that maximized the strong glass-forming contribution of glycerol, while minimizing its T-g lowering effect This quantitative evidence supports speculation about the fragility characteristics of these mixtures that has been ongoing for the past decade The DMA-based T-g and fragility determination method developed in this study represents a new approach for identifying optimal compositions for preservation of biologics.