Primary Drying: The Sublimation of Ice - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 103

and a range of processing conditions have shown that Equation (2) is in
most situations reasonably adequate for the prediction of t s .
Figure 4 illustrates an experimental test performed on 5% solutions of
KCl and polyvinyl pyrrolidone (PVP), both at 10-mm fill depth. The
inverse relationship between t s and T is clearly shown and, interestingly,
takes a very similar course for both products, despite their marked physical
differences, i.e. KCl is crystalline and PVP is amorphous. To a first
approximation, the sublimation rate increases 3-fold for every 101 rise in
temperature. It must, however, be remembered that for a wholly or partly
amorphous product, the temperature of the subliming ice front must not be
allowedtoexceedtheglasstransitiontemperatureT g .Itfollowsthatthe
product composition also plays an important role in determining t s .
The effect of chamber pressure on ice sublimation also needs to be
considered. It is shown for a particular case in Figure 5. Since gas
conduction (molecular collisions) accounts for the major contribution to
mass transfer (see Figure 2), an increase in pressure is expected to
accelerate sublimation. The upper limit is set by the SVP of ice, but there
is no advantage to be gained from evacuating the chamber to a pressure
substantially below the SVP.
The heat transfer coefficient K v increases with chamber pressure typi-
cally for pressures in excess of 10 Pa. The effect of chamber pressure on
the sublimation rate can be estimated. It is necessary, however, once again
Figure 4 Primary drying time dependence on the product temperature for a crystalline
(KCl) and an amorphous (PVP) product. Adapted from Pikal