The Dried Product - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 154

of temperatures (220-350 K) and concentrations (10-70% by weight)
for sucrose, a,a-trehalose, maltose and a- D -methyl glucoside. The fol-
lowing three questions were addressed:
(i) How do sugars affect the dynamics of water?
(ii) How do the dynamics of sugar molecules depend on the concen-
tration?
(iii) What conditions determine the ''transition'' into the vitreous
state?

The 13 C relaxation results led to the following conclusions:

Within the concentration (c)/temperature domain studied, sugar
molecules move as rigid bodies.
For c o 30%, the temperature dependence of the rotational corre-
lation time t follows the Arrhenius law.
At c 4 30%, the temperature dependence of t follows the VTF law,
Equation (5). The dependence of t on c is determined exclusively by
T o (c).
For temperatures below T o (c) þ 135 K, deviations from isotropic
tumbling become significant.
The temperature of zero mobility, T o , correlates well with the
calorimetric glass temperature T g , where T g ¼ (T o þ 20 K).
The -CH 2 OH groups display an additional, hindered rotation
about the symmetry axis. For c 4 30%, the ratio t ring /t CH2OH
increases strongly.

2

Results of H relaxation measurements at elevated pressures:

Up to c ¼ 30%, the isothermal pressure dependence of rotational
motion is anomalous; an increase in pressure produces an increased
water mobility.
At c 4 50%, the pressure dependence disappears.
The temperature dependence of t water follows the VTF law.
A hydration model, in which nearest water neighbours are con-
sidered to form a quasi-phase, suggests that ''hydration water''
performs anisotropic rotation.

2 H relaxation measurements at ambient pressures:

Results of

Up to c ¼ 40%, rotational motions of water decrease rapidly with
decreasing temperature.