Carbon-Deuterium Rotational-Echo Double-Resonance NMR Spectroscopy of Lyophilized Aspartame Formulations

In this study, changes in the local conformation of aspartame were observed in annealed lyophilized glasses by monitoring changes in the distance between two labeled sites using C-2H rotational-echo double-resonance (REDOR) nuclear magnetic resonance (NMR) spectroscopy. Confirmation that the REDOR experiments were producing accurate distance measurement was ensured by measuring the 13C-15N distance in glycine. The experiment was further verified by measuring the REDOR dephasing curve on 13C-2H methionine. 13C-2H REDOR dephasing curves were then measured on lyophilized aspartame-disaccharide formulations. In aspartame-sucrose formulation, the internuclear distances increased upon annealing, which correlated with decreased chemical reactivity. By contrast, annealing had only a minimal effect on the dephasing curve in aspartame-trehalose formulation. The results show that stability is a function of both mobility and local structure (conformation), even in a small molecule system such as lyophilized aspartame-sucrose. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:283-290, 2012