Secondary Drying: The Removal of Unfrozen Water - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 116

Figure 2 Isothermal drying profiles of Ficoll glass film of 0.08-mm thickness, where F is

defined as the fractional extent of drying, the mass of water removed at time t,
divided by the initial water content. Thus F ¼ 1 corresponds to the initial water
content, 8.87% in this case. Redrawn, with alterations, from ref. 119

has been established for freeze-dried preparations and also for the
evaporative drying of polymer films with different initial water contents,
as shown in Figure 2. 119 Thus, the independence of drying rate from
water content is a general property of plasticised glassy materials and is
not limited to disperse (freeze-dried) systems. The non-linearity of the
drying isotherms indicates that diffusion within the sample, and not
evaporation from the surface is the rate-limiting step. The analyses of
the isotherms also demonstrate that water is mobile in the glass, even
well below the measured glass transition.

9.5 Effects of Fill Depth and Cake Morphology

The specific surface area of the plug is generally quite large, typically up to
3m 2 g 1 , and will not only vary between different formulations but also
with processing history. For example, the specific surface area of the ice
crystals normally increases as does the cooling rate and, hence the degree
of undercooling. Thus, increasing the fill volume that will effectively lower
the cooling rate and therefore also the degree of undercooling would be