Secondary Drying: The Removal of Unfrozen Water - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 120

9.8 Operational Drying Protocols: Temperature
Ramping and Stepwise Heating

In practice, it is hardly possible to control the drying process exactly as
shown in Figure 4. A good compromise can however be achieved by
judicious temperature/time ramping, always keeping the drying

Figure 4 Optimal freeze-drying pathways for the preparation of a ''low-moisture'' sucrose
preparation. AB is the glass transition profile and CD the softening temperature
profile as observed by DSC. W g is the composition of the maximally freeze-
concentrated solution; ab is the ice sublimation at constant temperature; bcd is
the ideal secondary drying path; ( þ ) data from Shalaev; 121 and ( B ) data from
Shalaev and Franks 120 . For details, see text

Figure 5 Sketch of a practical secondary drying process, based on a stepwise temperature
ramping, interspersed with thermal equilibration periods, between the limits of
T g and T s . The process aims at a combination of economy of time with
acceptable product quality and is based on the extension of the ''ideal'' drying
protocol, shown in Figure 5