Physical Properties of Crystalline and Amorphous Solids - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 80

resulting mixture (excluding the crystalline ice phase) has then reached
its glass transition. This transition from a supersaturated, freeze-con-
centrated aqueous solution of very high viscosity to a brittle solid is
operationally characterised by a specific value of the glass transition
temperature. T g is therefore regarded as the temperature at which
freezing (at a measurable rate) is complete. Knowledge of T 0 g of a
particular formulation is of the utmost importance for the design of a
rational freeze-drying cycle because it is this temperature that should not
be exceeded during the removal of ice by sublimation. Its value depends
on the composition of the solid solution remaining at T g but is indepen-
dent of the concentration of the initial aqueous solution. At T 0 g , the solid
solution phase always contains a certain amount of unfrozen water that
can vary between 15% and 50% and can only be removed by its
diffusion to the surface, followed by desorption and transfer to the
condenser (secondary drying), see Chapter 9.
6.6 Materials Science of the Glass Transition: Its
Relevance to Freeze-Drying
Although the general features of vitreous states and the mechanisms of
their formation are identical for all materials, there are some aspects that
are of unique importance to freeze-drying technology, especially as
applied to pharmaceutical products.