Essential Physics of Low Temperature and Freezing - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 41

Figure 16 Transmission electron micrograph of a quench-frozen and etched 20% solution
of PVP. Grey areas correspond to prior positions ice crystals; their dimensions
are 100 nm. The solution phase (PVP þ unfrozen water) is confined to the

interstices between ice crystal; see bottom slide in Figure 14. Reproduced with
changes from Franks et al. 32

E

in neutron diffraction. 33 Although an increasing number of ice poly-
morphs that can exist under various pressure/temperature regimes have
been identified and their crystal structures established, only ''ordinary''
or hexagonal ice (ice-Ih) is of significance in the freeze-drying process.
This is the familiar form that is obtained when water in bulk is slowly
cooled to subzero temperatures. A comparison of the physical properties
of cold liquid water with those of ice-Ih demonstrates some of the
anomalies of H 2 O. Thus, freezing takes place with a volume expansion,
combined with a 50% reduction in the molar heat capacity. Both these
changes have implications in freeze-drying technology.
Whereas in the preceding sections of this chapter the emphasis has
been on ice nucleation and crystal growth, an aqueous solution, destined