Essential Physics of Low Temperature and Freezing - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 43

Figure 17 Solid-liquid phase diagram of the system water-tert-butanol; X ¼ mol fraction
concentration and P denotes a probable peritectic transition. A.2H 2 Oisa
stable crystalline hydrate, with T m ¼ 0.551C. The two eutectic points corre-
spond to 8.521C(x ¼ 0.065) and 4.551C(x ¼ 0.62). Adapted from
Takaizumi 35
are currently still subjects of intense research activity 37 and dispute. 169
Two ''states'' of amorphous water have been identified; they differ in
density and are formed by the rapid quenching of liquid water, by the
deposition of water vapour on cold surfaces, or by the compression of
hexagonal ice at low temperatures.
According to some researchers, the two states are in fact two distinct
phases, with real coexistence boundaries. 38 If this claim can ever be
verified, then it follows that there should exist a second critical point for
water, akin to the critical point at 3741C, where the liquid and gas
phases coalesce. It may, however, be impossible to confirm the existence
of such a point by experiment, because it would lie well below T hom ,
where freezing cannot be avoided.
While amorphous water as such may not figure in freeze-drying
technology, the opposite is true for many of the other components that
make up the finished pharmaceutical preparation. In fact, the realisation
of the importance of amorphism in pharmaceutical product develop-
ment has led to the birth of a new scientific discipline: pharmaceutical
materials science. Successful freeze-drying is firmly based on the same