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

## TL;DR

This study uses molecular dynamic simulations to better understand how molecular mobility in amorphous lactose changes with water content and temperature above the glass transition point.

## Contribution

The study introduces a novel method using RMSD and system size to quantify molecular mobility in amorphous lactose above Tg.

## Key findings

- Increased water activity and temperature enhance molecular mobility by expanding free volume and reducing energy barriers.
- Larger system sizes reveal emergent molecular mobility behaviors not seen in smaller systems.
- Water can shift from plasticizing to stabilizing effects, influencing molecular motion and clustering.

## Abstract

Measuring molecular mobility (Mm) in solid food is challenging due to the rigid and heterogeneous nature of these matrices. The thermodynamic parameter Strength (S) fails to account for molecular displacement distances. This study emphasizes the role of molecular dynamic (MD) simulation in quantifying Mm on amorphous lactose at mimic water activities (aw) at temperatures above the glass transition temperature (Tg), incorporating the S. The results show that coordinating root mean square displacement (RMSD) effectively quantifies Mm across different aw and temperature conditions. Both increased aw and higher temperatures facilitate Mm 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 Mm, as larger systems exhibit emergent behaviors that smaller systems cannot capture. The calculated MD relaxation time for 10,000-molecule lactose/water cells at a specific S 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.