title: Carbon-deuterium rotational-echo double-resonance NMR spectroscopy of lyophilized aspartame formulations.
abstract: 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-(2)H 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 (13)C-(15)N distance in glycine. The experiment was further verified by measuring the REDOR dephasing curve on (13)C-(2)H methionine. (13)C-(2)H 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, USA.
authors.forename: Suman A
authors.initials: SA
authors.lastname: Luthra
authors.forename: Marcel
authors.initials: M
authors.lastname: Utz
authors.forename: Eric M
authors.initials: EM
authors.lastname: Gorman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pikal
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Munson
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Lubach
mesh_terms: D001218:Aspartame / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003903:Deuterium / Q000737:chemistry*; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D005998:Glycine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008715:Methionine / Q000737:chemistry; D008968:Molecular Conformation; D014199:Trehalose / Q000737:chemistry
chemical_list: D002244:Carbon; D008715:Methionine; D003903:Deuterium; D014199:Trehalose; D005998:Glycine; D001218:Aspartame