The Importance of Understanding the Freezing Step and Its Impact on Freeze-Drying Process Performance

An Experimental-Based Approach to Construct the Process Design Space of a Freeze-Drying Process: An Effective Tool to Design an Optimum and Robust Freeze-Drying Process for Pharmaceuticals

“…Consequently, the majority of the optimization efforts are performed in this step. As reviewed in previous papers, 10,11 the freezing step has a significant effect on the primary drying rate; this is attributed to the morphology, and the number and size of ice crystals formed during the freezing step. The ice crystals leave a porous structure of dried product upon sublimation, which determines the permeability and resistance to water vapor flow through the dried product.…”

The Freeze-Drying of Foods—The Characteristic of the Process Course and the Effect of Its Parameters on the Physical Properties of Food Materials

“…To optimize the freeze-processes of liquid materials, the ice crystal sizes must be large enough to obtain the shortest primary drying time. The formation of numerous, small ice crystals during the freezing step leads to a high resistance to mass transfer in the dried product, whereas the formation of a few large ice crystals leads to small resistance [ 7 ]. However, to intensify the secondary drying period, these sizes need to be smaller to provide a large specific surface area for the dried matrix.…”

“…However, to intensify the secondary drying period, these sizes need to be smaller to provide a large specific surface area for the dried matrix. As a result, the desorption of non-frozen water from pores on the surface of the amorphous matrix proceeds faster [ 7 ]. Therefore, the method of freezing should be decided after analyzing the course of primary and secondary drying.…”

“…In the case of a cellular material that provides a high mass transport resistance, there are two cases for the use of this phenomenon. Evaporation can be facilitated when the material is naturally thin (e.g., vegetables or other deciduous plants) or in the case of a thin scrap of tissue with damaged cell membranes by cutting [ 7 ]. Another way to reduce mass transport resistance is by destroying cell membranes.…”

“…It is widely used for the stabilization of high-quality food, biological materials, and pharmaceuticals, such as proteins, vaccines, bacteria, and mammal cells. In the process, the quality of the dried product (biological, nutritional, and organoleptic properties) is retained [ 6 , 7 ]. This is due to the fact that freezing water in the material prior to lyophilization inhibits chemical, biochemical, and microbiological processes.…”