Dielectric spectroscopy of the low-losses sugar lyophilises: IV. Comparative study of four disaccharides at different moisture contents and temperatures

The purpose of this article is to study the effect of moisture content on the molecular dynamics of freeze-dried disaccharide excipients, in the context of understanding the instability of a pharmaceutical product. Four di-saccharides were measured by broad band dielectric spectroscopy, over a wide temperature range (-140 to +80 degrees C) with increasing moisture content from 1 to 7.5%. The two observed sub-Tg relaxation processes (beta and gamma) were affected by the moisture content, with a dramatic change in relaxation time of the beta-process, but only a moderate effect on the gamma-process. A suggestion of the likely arrangement of dipoles, and intra-molecular mobility, was performed in the framework of the free-space theory and based primarily on the analysis of the relaxation times, activation energies and Frohlich parameters. This analysis allows for some speculation concerning the disaccharide moisture buffering in freeze-dried formulations.

Automated summary

The effect of moisture content on the molecular dynamics of freeze-dried disaccharide excipients was studied to understand the instability of a pharmaceutical product. Four disaccharides were measured using broad band dielectric spectroscopy with increasing moisture content. The moisture content affected two sub-Tg relaxation processes: beta-process showed a dramatic change in relaxation time, while gamma-process had a moderate effect. The analysis of relaxation times, activation energies, and Frohlich parameters provided insights into the likely arrangement of dipoles and intra-molecular mobility.