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Updated: Feb 5, 2026

Sample Preparation by 3D-Correlative Focused Ion Beam Milling for High-Resolution Cryo-Electron Tomography
Published on: October 25, 2021
Correlation between molecular dynamics and physical stability of two milled anhydrous sugars: Lactose and sucrose
Geoff Smith1, Amjad Hussain2, Nadeem Irfan Bukhari2
1Leicester School of Pharmacy, De Montfort University, Leicester, UK.
Abstract:
The process of milling often results in amorphization and the physical stability of amorphous phase is linked with its molecular dynamics. This study focuses on a propensity of two disaccharides (lactose and sucrose) to amorphize on ball milling and the stability of the resultant amorphous phase. The amorphous content in milled sugars is estimated by Differential Scanning Calorimetry (DSC) and the stability was measured in terms of the tendency to recrystallize by Broadband Dielectric Spectroscopy (BDS). The results show that the amorphous content increases with milling time and is greater for lactose than sucrose. At the same degree of amorphization, sucrose recrystallize at temperature ∼15 °C higher than lactose, indicating higher stability. The molecular dynamics (beta relaxation process), suggest that milled sucrose is more stable with higher activation energy (∼9 kJ mol-1) than that of lactose. The moisture content of amorphous phase also impacts its molecular dynamics in terms of increase in activation energy as the moisture decrease with increasing the milling times. The study suggests a greater stability of amorphous sucrose and susceptibility of milled lactose to recrystallize, however, on extended milling when the moisture content decreases, lactose was seen to become relatively more stable.
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