ABSTRACT
This chapter is one of the shortest chapters ill this book; however, its brevity does not in any way detract from its importance in providing the concepts necessary for understanding some of the principles upon which the science of lyophilization is based. It is of fundamental importance to recognize that the entire lyophilization process is predicated on a series of phase changes:
liquid ~ solid (freezing), solid ~ gas (primary drying), and adsorbed state ~ gas (secondary drying). An understanding of the lyophilization process requires a comprehension of
these phase changes and how they relate to the nature of the formulation and interact with the operating parameters of the freeze-drying equipment. What makes lyophilization so deceptive is that it appears to be, as seen from the above, a relatively simplistic process. Its deception lies in the fact that it is often possible to obtain a dried product that meets the requirements for the potency of the active constituent and is within the required stability specifications without having a clear understanding of the mechanisms that are involved in the process. It would not be unusual if, in such cases, no rationale could be provided to substantiate that the product was actually lyophilized and not vacuum dried (Le., during the primary drying process there was significant mobile water present in the interstitial region of the matrix). Failure to provide the rationale for the lyophilization process will, for the most part, stem directly from a lack of knowledge of the various phase changes that occur during the process.
