Primary Drying: The Sublimation of Ice - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 107

Pa, is seen to be 0.16 g cm 2 h 1 at 201C. If the pressure is halved,
without a change in the shelf temperature, the product temperature falls
to 251C (B) and the process will therefore be accompanied by a
marked decrease in the sublimation rate. If, on the other hand, the
pressure is raised to 55 Pa, still at a constant shelf temperature, then the
sublimation rate increases to 0.19 g cm 2 h 1 , because the product
temperature rises to 17.51C, which is, however, well above T g and must
therefore be avoided. By changing the pressure, as well as the shelf
temperature, represented by point D, the sublimation rate can be
increased without danger of overheating the product.
It must be emphasised that the actual numerical values used in the
construction of Figure 6 are hypothetical and refer to a particular set of
conditions for product composition, vial type, fill depth, model of
freeze-drier and degree of shelf loading. However, similar diagrams
could be constructed for any freeze-drier/vial/loading combination.
Furthermore, Figure 6 takes no account of discontinuities in the
thermophysical properties of the product at T g . This discussion never-
theless serves to illustrate the general principle of interplay between shelf
Figure 6 Optimisation of the sublimation rate by the simultaneous control of shelf
temperature and chamber pressure. It is assumed that T g ¼ 201C. The
solution composition was as follows: recombinant human interleukin-1 receptor
antagonist, rhIL-1ra, in a solution of 2% w/v glycine, 1% w/v sucrose and 10
mM Na citrate buffer. Redrawn with changes from Chang and Fisher. 111 For
details see text