title: Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO 4 or NaH 2PO 4: Evidence for its Molecular Origin.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  The glass transition temperature (Tg) and the α-relaxation temperature (Tα) 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.
  
  
  RESULTS
  Thermal analysis measurements demonstrated that the addition of NaH2PO4 decreased both the glass transition temperature and the α-relaxation temperature of the dehydrated trehalose/NaH2PO4 mixture compared to trehalose alone while both Tg and Tα 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.
  
  
  CONCLUSIONS
  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 Tg of the mixtures than trehalose alone, creating large-sized ionic pockets, weakening interactions, and disrupting the original hydrogen-bonding network amongst trehalose molecules.
authors.affiliation: Department of Mechanical Engineering and Engineering Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, 28223, USA.
authors.forename: Lindong
authors.initials: L
authors.lastname: Weng
authors.forename: Gloria D
authors.initials: GD
authors.lastname: Elliott
mesh_terms: D002021:Buffers; D005898:Glass / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D010710:Phosphates / Q000737:chemistry*; D044366:Transition Temperature; D014199:Trehalose / Q000737:chemistry*; D058989:Vitrification
chemical_list: D002021:Buffers; D010710:Phosphates; D014199:Trehalose; C018279:sodium phosphate