The Process Sequence in Summary - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 16

error. 13 We hope that this common view will be dispelled in the follow-
ing chapters. Indeed, it is the main purpose of this topic to demonstrate
that almost all freeze-dried products can be made with high yields, be
easy to rehydrate and, depending on the formulation, possess an
acceptable shelf life under ''room temperature'' storage conditions. A
state-of-the-art understanding of the interplay between the formulation
and the three controllable process variables (shelf temperature, chamber
pressure and time) allows the design of efficient processes to produce
high-quality products in acceptable yields.

2.2 Drying Process: Coupled Heat and Mass Transfer

The basic process simply requires that sufficient heat is supplied to the
product via the shelves to exactly balance the heat absorbed by the
sublimation of the ice, i.e. heat supplied to the product ¼ heat required
for sublimation:

K v (T s - T p ) ¼ DH s (dm/dt) (1)

where K v is a heat transfer coefficient, T s the shelf temperature and T p
the product temperature. DH s is the heat of sublimation of ice at T p and
dm/dt is the rate of mass transfer of water vapour from the chamber to
the condenser surface. The significance and estimation of the various
quantities in Equation (1) will be discussed in detail in Chapter 8.
Heat transfer occurs by a combination, not necessarily of a linear
nature, of three mechanisms:
(i) radiation, mainly from the walls and the door of the freeze-drier;
(ii) conduction by direct contact between solid and/or liquid inter-
faces, i.e. shelf/container and container/solution;
(iii) convection through the gas phase (collisions between gas mole-
cules).

The relative contribution of each mechanism to K v depends on many
factors, also to be discussed in Chapter 8.
Mass transfer (water) depends on

fill depth (cake thickness);
total solid content;
cake porosity (governed mainly by ice crystal size distribution);
surface area from which sublimation can occur.

All these factors help to determine the resistance to sublimation.