Comparison of the Glass Transition Temperature and Fragility Parameter of Isomalto-Olygomer Predicted by Molecular Dynamics Simulations with Those Measured by Differential Scanning Calorimetry

Abstract

The purpose of this study is to examine whether molecular dynamics (MD) simulations using a commercially available software for personal computers can estimate the glass transition temperature (T_g) of amorphous systems containing pharmaceutically-relevant excipients. MD simulations were carried out with an amorphous matrix model constructed from isomaltoheptaose, and the T_g estimated from the calculated density versus temperature profile was compared with the T_g measured by differential scanning calorimetry (DSC) for freeze-dried isomalto-oligomer having an average molecular weight close to that of isomaltoheptaose. The T_g values determined by DSC were lower by 10 to 20 K than those extrapolated from the T_g values estimated by MD simulation. Fragility parameter was estimated to be 56 and 51 from MD simulation and from DSC measurement, respectively. Thus, the results suggest that MD simulation can provide approximate estimates for the T_g and fragility parameter of amorphous formulations. However, a reduction of the cooling rate, achievable by sufficiently elongating the simulation duration, is necessary for more accurate estimation.