Historical Background - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 10

discussed in more detail in Chapters 5 and 11. It will now be apparent that
the freezing (concentration) of a solution must increase the probability of
random collisions, which can accelerate aggregation, leading eventually to
precipitation. In practice it is more important to know whether, on
reconstitution in aqueous solution, and at the point of use, the bioactive
state is rapidly regained.
1.4 Why Freeze-Dry?
Having once accepted the consensus view that ''dry'' is indeed synon-
ymous with ''stable'', the question arises why the drying process needs to
be performed by the circuitous route of freezing, followed by sublima-
tion of ice. On the basis of the total energy balance, a standard process
cycle necessitates several cooling and heating processes. When compared
to a simple evaporation of water, say at 37 1 C, freeze-drying as a means
of removing water, must be regarded as an extremely wasteful utilisation
of energy. There are several additional cost factors to be considered, and
the ''true'' cost of freeze-drying is examined in Chapter 10. The follow-
ing question may well be posed: why has freeze-drying become the
universally preferred method of rendering pharmaceutical products
stable? It is interesting that several of the reasons advanced are based
on misconceptions, while others rely only on marketing wisdom.
The following summary gives the main responses that have been
advanced by seasoned industrial managers when posed the question:
why freeze-dry?
Low temperatures protect the active material during processing.
Freeze-drying is a process that is approved by regulatory author-
ities.
Freeze-drying can be performed under sterile conditions.
The dried product can be rapidly rehydrated.
The finished product format (a low-density, porous plug) is recog-
nised and accepted by end users.
Freeze-drying is associated with quality.
Freeze-drying has the reputation of being simple to perform.
It has been successfully used by other companies and/or for other
products.
This type of product has always been freeze-dried.
It is seen that the reasons advanced are indeed a strange mixture. They are
listed here in no particular order of significance or veracity. The most