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

Abstract

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 disaccharides were measured by broad band dielectric spectroscopy, over a wide temperature range (−140 to +80 °C) with increasing moisture content from 1 to 7.5%. The two observed sub-Tg relaxation processes (β and γ) were affected by the moisture content, with a dramatic change in relaxation time of the β-process, but only a moderate effect on the γ-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.