Scale-Up of Freeze-Drying Cycles, the Use of Process Analytical Technology (PAT), and Statistical Analysis

Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design Space Determination of Freeze-Drying Processes

“…Otherwise, cake collapse takes place, leading to misestimation of the R p profile. If this happens, product temperature during primary drying will be also misestimated and the resulting design space will not ensure product quality (14).…”

“…An empirical approach can be performed by a non-expert practitioner, but it requires many time-consuming experiments to determine the relationship between the operating conditions and the resulting process. Besides, this approach is only valid in situ, which limits the scalability of the results found at lab-scale, where these experiments may be carried out (13,14). Mechanistic approaches, on the other hand, allow mathematical modelling of the product temperature, water vapor flow and drying time throughout a process as a function of the chamber pressure and shelf temperature (15)(16)(17)(18).…”

Use of a temperature ramp approach (TRA) to design an optimum and robust freeze-drying process for pharmaceutical formulations

“…In a recent study by Bourles et al (Bourlès et al, 2019), the use of an experimental approach (based on a statistical model) was detailed to construct and optimize the primary drying section, where these authors used a design of experiments (DoE) to obtain the necessary input parameters to the statistical model. Similar to the current study and a previous study (Assegehegn et al, 2020), Bourles et al considered the edge vial effect during the construction of the design space, demonstrating its importance to design a robust freeze-drying process.…”

“…Similar to the current study and a previous study (Assegehegn et al, 2020), Bourles et al considered the edge vial effect during the construction of the design space, demonstrating its importance to design a robust freeze-drying process. Although construction of an experimental-based design space requires several experimental setups (Bourlès et al, 2019), results obtained using an experimental approach are more reliable than those obtained using mathematical models (Assegehegn et al, 2020). In contrast, the TRA developed in this study uses few experimental studies to define optimum processing conditions of a given formulation during primary drying.…”

Drying Behaviors of Mint Leaves in Vacuum Freeze Drying

“…This process reduces the rate of thermal and chemical degradation. It limits the microbiological activity keeps the original taste and aroma in dried nutrition products and provides products with excellent structural bonding properties [5][6][7][8]. Despite these advantages, because of its complexity, high capital investment and operating costs, its uses are mostly restricted to heat-sensitive materials with high value [1].…”