The Principles of Freeze-Drying and Application of Analytical Technologies.

Freeze-drying is a complex process despite the relatively small number of steps involved, since the freezing, sublimation, desorption, and reconstitution processes all play a part in determining the success or otherwise of the final product qualities, and each stage can impose different stresses on a product. This is particularly the case with many fragile biological samples, which require great care in the selection of formulation additives such as protective agents and other stabilizers. Despite this, the process is widely used, not least because once any such processing stresses can be overcome, the result is typically a significantly more stable product than was the case with the starting material. Indeed, lyophilization may be considered a gentler method than conventional air-drying methods, which tend to apply heat to the product rather than starting by removing heat as is the case here. Additionally, due to the high surface area to volume ratio, freeze-dried materials tend to be drier than their conventionally dried counterparts and also rehydrate more rapidly. This chapter provides an overview of freeze-drying (lyophilization) of biological specimens with particular reference to the importance of formulation development, characterization, and cycle development factors necessary for the commercial exploitation of freeze-dried products, and reviews the recent developments in analytical methods which have come to underpin modern freeze-drying practice.