Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO 4 or NaH 2PO 4: Evidence for its Molecular Origin.
Distinctly Different Glass Transition Behaviors of Trehalose Mixed with Na2HPO 4 or NaH 2PO 4: Evidence for its Molecular Origin.
复制标题
DOI：
10.1007/s11095-014-1610-1
复制
发表时间：
2015-07
影响因子：
3.7
通讯作者：
Elliott GD
中科院分区：
文献类型：
--
作者：
Weng L;Elliott GD
本研究旨在了解糖分子和磷酸盐离子之间的相互作用如何影响其混合物的玻璃化转变温度，以及对药物配方的影响。用差示扫描量热法和动态力学分析分别测定了脱水海藻糖/磷酸钠（一碱和二碱）混合物的玻璃化转变温度（Tg）和α-弛豫温度（Tα）。分子动力学模拟研究了糖分子与磷酸离子之间的微观相互作用。对这些混合物的氢键特性和自聚集特性进行了量化和比较。热分析结果表明，与单独添加海藻糖相比，添加NaH2PO4降低了脱水海藻糖/NaH2PO4混合物的玻璃化转变温度和α-弛豫温度，而添加Na2HPO4可提高纯海藻糖的Tg和t - α。发现海藻糖与HPO42−之间的氢键相互作用比海藻糖-海藻糖之间的氢键和海藻糖与H2PO4−之间形成的氢键相互作用更强。与H2PO4 -离子相比，HPO42 -离子聚集成更小的簇。海藻糖/Na2HPO4混合物比纯海藻糖产生更高的Tg，因为边缘自聚集的HPO42−离子与海藻糖分子建立了强化的氢键网络。相比之下，H2PO4−离子仅作为增塑剂，导致混合物的Tg比单独的海藻糖低，产生大尺寸的离子口袋，削弱相互作用，破坏海藻糖分子之间原有的氢键网络。
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 (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. 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 HPO42− were found to be stronger than both the trehalose-trehalose hydrogen bonds and those formed between trehalose and H2PO4−. The HPO42− ions also aggregated into smaller clusters than H2PO4− ions. The trehalose/Na2HPO4 mixture yielded a higher Tg than pure trehalose because marginally self-aggregated HPO42− 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.