Quantitative Analysis of Molecular Mobility in Amorphous Lactose Above Tg: A Novel Insight from Molecular Dynamic Simulation to Strength Parameter

Measuring molecular mobility (<i>M_m</i>) in solid food is challenging due to the rigid and heterogeneous nature of these matrices. The thermodynamic parameter <i>Strength</i> (<i>S</i>) fails to account for molecular displacement distances. This study emphasizes the role of molecular dynamic (<i>MD</i>) simulation in quantifying <i>M_m</i> on amorphous lactose at mimic water activities (<i>a_w</i>) at temperatures above the glass transition temperature (<i>T_g</i>), incorporating the <i>S</i>. The results show that coordinating root mean square displacement (<i>RMSD</i>) effectively quantifies <i>M_m</i> across different <i>a_w</i> and temperature conditions. Both increased <i>a_w</i> and higher temperatures facilitate <i>M_m</i> by expanding free volume and reducing energy barriers for molecular rearrangement, as indicated by the mobility coefficient calculations. This study also emphasizes the importance of system size in interpreting <i>M_m</i>, as larger systems exhibit emergent behaviors that smaller systems cannot capture. The calculated <i>MD</i> relaxation time for 10,000-molecule lactose/water cells at a specific <i>S</i> value was successfully translated to a real timescale of 1.8 × 10⁶ s, consistent with experimental data (1.2 × 10⁶ s). Moreover, water can shift from a plasticizing role to a more stabilizing one, slowing molecular motion and leading to equilibrium clustering. These findings have important implications for understanding the behavior of amorphous lactose in food and pharmaceutical formulations.