The aim of this paper is to review the effects of several different types of freeze-drying processes on some nutritional properties of foodstuff. Both the vacuum freeze-drying (VFD) process and the atmospheric freeze-drying (AFD) process have been considered, as well as the possibility of accelerating both using ultrasound (US), microwave (MWD), infrared (IR) heating, and other techniques. The effects of these processes on ascorbic acid, phenolic compounds, and total antioxidant capacity have been extensively reviewed in this paper, as these molecules were widely investigated in the literature. Finally, a summary of effects on other less recurrent studied compounds is also presented. It appears that for vitamin C, VFD most of the time gives the best results; MWD and IR combined processes with VFD seem to be able to decrease processing time, while having a mild effect on product quality. With respect to phenolic compounds and total antioxidant capacity, VFD and AFD seem to have fairly similar effects, with a mild effect of IR and US.

This article is focused on the methods based on the pressure rise test (PRT) used to monitor the primary drying of a lyophilization process. Details about the model-based algorithms proposed to interpret the PRT, namely, manometric temperature measurement (MTM), pressure rise analysis (PRA), and dynamic parameters estimation (DPE), are briefly summarized and various features of the models used by these algorithms, in particular the role of the vial wall and radiation on the thermal balance of the system, are investigated. The optimal selection of the sampling frequency and the time interval between two tests is discussed, and the influence of the duration of the test on the results is investigated by means of mathematical simulation: results obtained from the PRT can be significantly improved by optimizing the duration of the test. Moreover, the problem of misleading results obtained at the end of the primary drying is investigated, taking into account the problem of ill-conditioning of the algorithms. An improved version of the DPE algorithm is proposed to cope with this problem; its effectiveness is demonstrated by means of mathematical simulations and experimental runs.

Purpose: This paper shows how to optimize the primary drying phase, for both product quality and drying time, of a parenteral formulation via design space. Methods: A non-steady state model, parameterized with experimentally determined heat and mass transfer coefficients, is used to define the design space when the heat transfer coefficient varies with the position of the vial in the array. The calculations recognize both equipment and product constraints, and also take into account model parameter uncertainty. Results: Examples are given of cycles designed for the same formulation, but varying the freezing conditions and the freeze-dryer scale. These are then compared in terms of drying time. Furthermore, the impact of inter-vial variability on design space, and therefore on the optimized cycle, is addressed. With this regard, a simplified method is presented for the cycle design, which reduces the experimental effort required for the system qualification. Conclusions: The use of mathematical modeling is demonstrated to be very effective not only for cycle development, but also for solving problem of process transfer. This study showed that inter-vial variability remains significant when vials are loaded on plastic trays, and how inter-vial variability can be taken into account during process design.