Essential Physics of Low Temperature and Freezing - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 25

Figure 5 The effect of temperature on pK a of some acids used in the preparation of pH
buffers, normalised to 301C. Reproduced from Franks, 17 with permission from
Cambridge University Press

for freeze-drying. As shown, carbonate-type buffers are particularly
sensitive to subzero temperatures, whereas acetates show little change
in pH in the temperature range of relevance to freeze-drying.
As also shown in Figure 4, the transport properties of water display a
strongly non-Arrhenius behaviour at subzero temperatures. Thus, the
viscosity of water, when extrapolated to 901C, is of the same order as
that of glycerol at room temperature. This rapid viscosity rise at low
temperatures plays a role in limiting the cooling rates that can be
achieved in practice.

4.4 Ice: Its Nucleation in Undercooled Water

The occurrence of a phase transition requires a prior nucleation of the
daughter phase within the mother phase. Thus, the growth of crystals in
a saturated solution requires the prior generation of nuclei, composed of