Glass Transition Temperature of Glucose, Sucrose, and Trehalose:  An Experimental and in Silico Study

Abstract

Isothermal-isobaric molecular dynamics simulations are used to calculate the specific volume of models of different amorphous carbohydrates (glucose, sucrose, and trehalose) as a function of temperature. Plots of specific volume vs temperature exhibit a characteristic change in slope when the amorphous systems change from the glassy to the rubbery state. The intersection of the regression lines of data below (glassy state) and above (rubbery state) the change in slope provides the glass transition temperature (T(g)). These predicted glass transition temperatures are compared to experimental T(g) values as obtained from differential scanning calorimetry measurements. As expected, the predicted values are systematically higher than the experimental ones (about 12-34 K) as the cooling rates of the modeling methods are about a factor of 10(12) faster. Nevertheless, the calculated trend of T(g) values agrees exactly with the experimental trend: T(g)(glucose) < T(g)(sucrose) < T(g)(trehalose). Furthermore, the relative differences between the glass transition temperatures were also computed precisely, implying that atomistic molecular dynamics simulations can reproduce trends of T(g) values in amorphous carbohydrates with high quality.

Coalescence-based assessment of aerosol phase state using dimers prepared through a dual-differential mobility analyzer technique

“…In this experiment, D mono D 50 nm, D c D 60.9 nm § 2.5 nm observed at T »70 C, D uc D 65.7 nm § 0.5 nm observed at T < 50 C, and transition diameters corresponding to partially coalesced particles are observed between 50 C and 70 C. The relaxation temperature (T r ) was measured as 63.7 C § 4.4 C. This temperature is higher than the 60 C glass transition temperature (T g ) of amorphous sucrose estimated from differential scanning calorimetry data (Simperler et al 2006), as would be expected for a less viscous particle. However, the observed difference is within measurement uncertainties in either measurement.…”

Empirical and theoretical models of equilibrium and non-equilibrium transition temperatures of supplemented phase diagrams in aqueous systems (IUPAC Technical Report)

“…The same criteria to determine T g , but using NPTMD was reported for maltodecaose (w 2 = 0.84-0.99) aqueous solutions [148]; glucose and isomaltodecaose (in the pure form and hydrated with one molecule of water) [149]; pure cellulose [150]; pure myo-and neo-inositol [151]; pure glucose, sucrose, and trehalose [152]; trehalose (w 2 = 0.95-1.00) aqueous mixtures [153]; and glycerol [154]. Figure 7 shows the experimental and calculated T g of concentrated aqueous trehalose solutions as a function of concentration on the very concentrated region (w 2 > 0.92) where MD simulations are available.…”

“…The coarse grain model for carbohydrates (denoted M3B), applied by Molinero et al [156] for glucose, represents each glucose monomer by three beads while describing the water molecule as a single particle. The M3B model includes no charges or hydrogen-bonding terms, predicted by NPTMD ( ) [153], compared to experimental data ( ) [7,92,123,126], ( ○ ) [152].…”

“…Glass transition temperature of glucose vs. mass fraction of glucose in glucose aqueous solutions as predicted by MD ( ) [146], NPTMD ( ) [152], and CGMD ( ) [155], compared to experimental data (solid line) [157].…”

Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

“…To date, a number of molecular mechanics (MM)-based molecular dynamics (MD) simulation studies [9][10][11][12] have been performed to study various molecules (e.g. dissolution of the molecules from the crystal surface) 13 or to identify drug-polymer miscibility in solid dispersions [14][15][16][17][18] . Recently, we 19 reported the use of quantum mechanical (QM) calculations with commercially available software (Gaussian 09) to characterise possible drug/polymer interactions.…”