A Direct Characterization Method of the Ice Morphology. Relationship Between Mean Crystals Size and Primary Drying Times of Freeze-Drying Processes

Abstract

In the freeze-drying process, the freezing step is one of the most important steps which determines the texture of the frozen material and, consequently, the final morphological characteristics of the freeze-dried material and its biological activity and its stability. As a matter of fact, the parameters of the freezing protocol have a direct effect on the pore size distribution and on the pore connectivity of the porous network of the freeze-dried matrix. Thus, the ice crystal morphology determines indirectly the mass and the heat transfer rates through the dry layer and, consequently, the freezing parameters have a strong influence on the total duration of the primary and secondary sublimation steps. The main objective of this study was to adapt and to develop a new optical direct microscopy method, based on the reflected flux differences, with episcopic axial lighting to characterize the structure of the different phases of a standard pharmaceutical matrix used for pharmaceutical proteins free...