Biomedical Engineering Reference
In-Depth Information
Freeze drying cycle
Secondary
drying
Freezing
Primary drying
Time (h)
Shelf temperature
Product temperature
Figure
13.8.
Genericized freeze-drying cycle.
attributes [40]. Key aspects of the lyophilization cycle (Fig. 13.8) must include
maintaining the product temperature below its collapse temperature T
c
during freeze-
drying, which is the temperature at which freeze-dried cake will collapse. The primary
drying phase of the process (sublimation of ice under vacuum) is the longest step, but must
be optimized to be as short as possible, as this adds time and cost to the process.
The secondary drying phase (desorption of water from the product under high vacuum
and high product temperature) must not start until the primary drying is completed, as this
may take the product temperature above T
c
during primary drying.
The application of PAT tools in freeze-drying covers a verywide range of usage. One
of the reasons for this is that the full operating conditions of the full-scale commercial
manufacturing freeze-dryer can be duplicated easily in off-the-shelf scaled-down free-
ze-dryers and the physical conditions of cooling and heating, reduced pressure under
vacuum, and purging with inert gases can all be executed in model systems directly
linked to PAT-like tools [41].
13.5.8 Freezing
Freezing has been studied extensively to understand ice formation, crystallization, and
amorphous state of API and excipients. The rate of freezing can influence ice formation,
