Collapse unfrozen water

Fig. 1.73.3. DR as a function of drying time of 10% mannitol solution frozen in LN2 in 130 vials. Plot 1 product is collapsed because 380 vials have been loaded (also confirmed by visual inspection of the dry product) after a short time ofSD, the water evaporates with difficulty from the highly viscous concentrates. Plot 3 in liquid nitrogen frozen at a rate of 30-60 °C/min, below DR = 0.3%/h the unfrozen water in viscous inclusions is difficult...

Collapse in freeze-drying occurs above a critical temperature, which allows viscous flow of freeze-concentrated amorphous solutes (Bellows and King 1973) as they are plasticized by unfrozen water (Roos 2004). The onset temperature of ice melting, T, can be used as a critical reference temperature for production of properly freeze-dried materials. 

It is harder to remove the unfrozen water trapped in an amorphous solid. So after primary drying, a secondary drying stage removes that water by increasing the temperature. The final temperature of this secondary process is the key factor in determining residual moisture in the dried cake. The pressure is kept the same for secondary and primary drying to avoid protein collapse. The ideal result is a porous cake with little residual moisture. Porosity is important in later reconstituting the product. 

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