Freeze-drying: A relevant unit operation in the manufacture of foods, nutritional products, and pharmaceuticals.

Freeze-drying, a drying unit operation frequently used in food, pharmaceutical, and biopharmaceutical industries to prolong the shelf life of labile products, is an energy-intensive, time-consuming, and expensive process. Although all three steps (freezing, primary drying, and secondary drying) of freeze-drying are important, primary drying is the longest and most critical one. As sublimation during primary drying is mainly described in terms of heat and mass transfer, the present work provides extensive theoretical and experimental analyses of these processes. First, a detailed review of the current state-of-the art of freeze-drying, focusing on the drying stage, is given, which contributes to a fundamental understanding of the drying process. Second, a detailed experimental study of the drying section of the freeze-drying process is discussed, furnishing information on the relationship between input and output process parameters during the primary drying stage and thus aiding freeze-drying process design and optimization. In this regard, the influence of primary drying input parameters (i.e., shelf temperature and chamber pressure) and vial position on output parameters such as product temperature, sublimation rate, overall vial heat transfer coefficient, and resistance to mass transfer of the dried product are extensively discussed. For all combinations of shelf temperature and chamber pressure studied herein, the highest product temperature, sublimation rate, and overall vial heat transfer coefficient are observed in front edge vials, whereas the lowest values are observed in center vials. In general, the highest sublimation rate, at a given product temperature, is observed for low chamber pressure-high shelf temperature combinations.