Secondary Drying The Removal of Unfrozen Water

After a multicomponent aqueous solution has been freeze-concentrated to the limit and the ice has been sublimed, any residual unfrozen water must be removed from the remaining solid solution by diffusion, desorption and evaporation (transfer to the condenser). This process is termed secondary drying . For an amorphous preparation, the amount of unfrozen water remaining after the removal of ice may be typically 20-30% w/w, but much higher values, even >50% w/w, have been found in some formulations. Attempts are on record to measure the amount of water that remains in the freeze-concentrated solution phase at 7, mainly by differential scanning calorimetry but such... 

Although the process of unfrozen water removal from the material, subsequent to ice sublimation, is commonly referred to as desorption , this is misleading. It has been shown that the residual water forms a mobile component of a solid solution, so that diffusion more correctly describes the mechanism of its removal. Compared to the diffusion rate of water from the bulk to the surface, its eventual desorption from the surface is rapid and can in practice almost be neglected. As will be shown later, secondary drying kinetics can be modelled adequately by standard treatments of diffusive processes. The effects of many variables on the kinetics of secondary drying may be found in Pikal et al ... 

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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