Paper Citing NAMD - Abstract
Weng, Lindong; Elliott, Gloria D.
Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO4 or NaH2PO4: Evidence for its Molecular Origin
PHARMACEUTICAL RESEARCH, 32:2217-2228, JUL 2015
The present study is aimed at understanding how the interactions between sugar molecules and phosphate ions affect the glass transition temperature of their mixtures, and the implications for pharmaceutical formulations. The glass transition temperature (T (g) ) and the alpha-relaxation temperature (T (alpha) ) of dehydrated trehalose/sodium phosphate mixtures (monobasic or dibasic) were determined by differential scanning calorimetry and dynamic mechanical analysis, respectively. Molecular dynamics simulations were also conducted to investigate the microscopic interactions between sugar molecules and phosphate ions. The hydrogen-bonding characteristics and the self-aggregation features of these mixtures were quantified and compared. Thermal analysis measurements demonstrated that the addition of NaH2PO4 decreased both the glass transition temperature and the alpha-relaxation temperature of the dehydrated trehalose/NaH2PO4 mixture compared to trehalose alone while both T (g) and T (alpha) were increased by adding Na2HPO4 to pure trehalose. The hydrogen-bonding interactions between trehalose and HPO4 (2-) were found to be stronger than both the trehalose-trehalose hydrogen bonds and those formed between trehalose and H2PO4 (-). The HPO4 (2-) ions also aggregated into smaller clusters than H2PO4 (-) ions. The trehalose/Na2HPO4 mixture yielded a higher T (g) than pure trehalose because marginally self-aggregated HPO4 (2-) ions established a strengthened hydrogen-bonding network with trehalose molecules. In contrast H2PO4 (-) ions served only as plasticizers, resulting in a lower T (g) of the mixtures than trehalose alone, creating large-sized ionic pockets, weakening interactions, and disrupting the original hydrogen-bonding network amongst trehalose molecules.
