Secondary Drying: The Removal of Unfrozen Water - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 121

temperature between the limits set by T g and T s . The temperature separa-
tion DT ¼ (T s - T g ) is typically of the order of 10 K (see Figure 4). The
underlying principle of the method is illustrated in Figure 5a of Chapter 6,
and a qualitative sketch of a recommended time/temperature protocol for
secondary drying is shown in Figure 5, beginning at T g and ramping of the
shelf temperature in steps of ca. þ 51Ch 1 . Assuming that the formulation
and fill depth do not exceed the recommended values, this protocol should
normally allow enough time for sufficient water to be removed from the
product to raise the glass temperature of the plug to the set shelf temper-
ature. The plug will thus never be exposed to temperatures in excess of
(T g þ 10 K) for unduly long periods.