Heat and Mass Transfer in Low Pressure Gases: Applications to Freeze Drying

Freeze drying or ‘‘lyophilization’’ is a drying process in which the solvent, normally water, is first frozen and then removed by sublimation in an environment of low pressure-typically in the range 0.05-0.5 torr (6.6-66 Pa). In the pharmaceutical industry, the aqueous solution is first filled into suitable containers, usually glass vials, and the filled vials are loaded onto temperature-controlled shelves contained in a large ‘‘vacuum-tight’’ drying chamber. The temperature of the shelves is lowered to remove heat from the solution and ultimately transform most of the water to ice. The drug and excipients may also crystallize during this freezing stage. More often the solutes remain amorphous and are ‘‘freeze concentrated’’ into a rigid pseudosolid, or glass, which typically also contains roughly 20% unfrozen water.