Primary Drying: The Sublimation of Ice - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 104

Figure 5 Effect of chamber pressure on sublimation rate. Fill volume: 2 ml; vial diameter:
2.54 cm 2 . Adapted from Pikal

to take into account the various mechanisms by which heat is transferred
between the shelf surface and the subliming ice front.
It is good practice to adjust the chamber pressure (but keeping below
the SVP of water vapour over ice at the drying temperature) by a dry,
non-condensing gas bleed (nitrogen, argon and helium). As a generalisa-
tion the pressure might be set close to, but not exceeding, the SVP of
water over ice at the product temperature. A typical relationship between
the sublimation rate and chamber pressure is shown in Figure 5. If the
pressure is allowed to fall too far, then the rates of heat transfer into the
product will no longer ''balance'' the rate of mass transfer and the
product temperature will decrease (sublimative cooling). For reasons of
process efficiency, the chamber pressure should probably not be allowed
to drop to below 50% of the SVP at the relevant temperature.

8.4 Influences of Formulation and Freezing Procedure

on Ice Sublimation

There are additional factors to be taken into account that influence t s ,
and also the quality and uniformity of products freeze-dried in vials:

ice crystal size distribution;
solid content (solution concentration);