General Principles of
Freeze Drying (The Lyophilization Process)
Freezing
Upon completion of product freezing, the product
will have acquired a frozen structure, which cannot be changed
during freeze drying. Sublimation, and the qualities of the
finished product are greatly dependent on this crystal structure.
In fact, it is considered the most crucial stage of the freeze
drying process.
Speed of Freezing
On the pilot level, fast or very fast freezing
is relatively easy to achieve. However, for industrial production
settings, freezing at the same rates is unrealistic because
of the problems of product preparation (filling, loading time)
and larger systems costs will dictate compromises in the same
process. From Fig 1 we observe:
As soon as the product reaches 0° C (Point
A on the curve of Fig 1), some of the particles transform to
ice. This is the nucleation process. Generally, biological products
contain between 80% and 95% water.
Observe that the temperature of the product stabilizes
after time period at about 0° C.
At Point B, the ice crystals previously formed
have expanded, and consist practically of pure water.
At Point C, the crystals have grown larger, and
now occupy 80% to 90% of the initial volume of the solution.
The crystallization of the free water is nearly complete. These
crystals seem to be contained in an interstitial state, still
liquid, but which constitutes the principal active element of
the solution.
At Point D, the interstitial component itself
has reached freezing temperature, and the amorphous appearance
is even more apparent, and a barely visible “skin”
has formed on the surface. This structure is ideal for sublimation.
We now have a paradoxical situation: a slow cooling
which can lead to a rapid coagulation of the constituent water.
In many cases, freezing induced by these conditions may be necessary
to achieve successful freeze drying of a sensitive product.
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