ABSTRACT
The principal function of the primary drying process is to reduce a major quantity of solvent in a product while the matrix is in a frozen state (i.e., when the mobility of the water in the interstitial region approaches zero). For an aqueous formulation, the water is removed by the sublimation of ice crystals. If the mobility of the water in the interstitial is > 0 during the primary drying process, then, after sublimation of the ice crystals, there can be a lack of rigidity of the exposed interstitial region and collapse or even meltback can occur, as illustrated in Figure 1.3c. It will be shown that the chamber pressure and shelf-surface temperature necessary to complete the primary drying process will be determined by the thermal characteristics of the formulation, mainly the collapse temperature and occasionally the eutectic temperature. There is a tendency to departmentalize a given process, and lyophilization is not an exception. The reader should be aware at the start that, after removal of the ice crystals from the matrix, the secondary drying commences, and some water vapor is also removed from the exposed interstitial region of the matrix. As a result, there is no sharp demarcation between the completion of primary drying and the commencement of secondary drying.
