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Freeze-drying has always been considered an extremely expensive procedure to dehydrate food or pharmaceutical products, and for this reason, it has been employed only if strictly necessary or when the high added value of the final product could justify the costs. However, little effort has been made to analyze the factors that make this technology so unaffordable. In this work, a model was proposed to calculate in detail the operational (OC) and capital costs (CC) of a freeze-drying cycle and an evaluation of the process bottlenecks was made. The main result is that the process itself, contrary to the classic belief, is not the most expensive part of freeze-drying, while the initial investment is the real limiting factor. Under this consideration, the optimization of a freeze-drying cycle should be formulated in order to fit more cycles in the lifespan of the apparatus, instead of merely reducing the power consumption of the machine.

Continuous manufacturing is becoming increasingly important in the pharmaceutical industry, and lyophilization, as a downstream process, is actively involved in the process of transition from batch to continuous. This chapter summarizes the main drawbacks of batch lyophilization and their impact on the production of pharmaceutical and biotech drugs, as well as the potential advantages resulting from the application of continuous manufacturing strategies. Attention is then given to three recent technologies, which have a great deal of potential to improve the quality and uniformity of the finished products and enhance process efficiency and profitability.

In response to the current trend in the pharmaceutical industry, a new concept for the freeze-drying of pharmaceuticals in unit-doses is presented: the continuous freeze-drying/lyophilization of suspended vials. This configuration makes it possible to set up a continuous freeze-drying process that produces a final product with similar characteristics to those traditionally obtained by means of the batch process but which avoids the drawbacks of conventional, batch freeze-drying. The feasibility and advantages of this new concept are presented in this work. Continuous freeze-drying has been found to improve heat transfer uniformity and reduce the primary drying duration by 2-4 times. As far as the structure of lyophilized products is concerned, SEM micrographs of the lyophilized samples showed that this technology improves vial-to-vial and intravial homogeneity.

A multi-scale approach can be used to simulate the drying behavior of microparticles in packed-bed. Data outcomes from discrete element method (DEM) and computational fluid dynamics (CFD) simulations can be used to estimate some relevant product characteristics, such as the porosity, tortuosity, voids in the bed and permeability which are required by the multi scale model. Data from DEM simulations are presented, with a particular focus on the influence of the model parameters, packing characteristics and inhomogeneities (wall effect and particles segregation); computational costs and scala bility are also considered. Data on the properties of packings as modeled at the macroscale are presented with regard to the thermal conductivity of gases in the Knudsen regime and effective properties of packed-beds modeled as a pseudo-homogeneous medium. A mathematical model of the freeze-drying of single microparticles and its outcomes are first presented. Data outcomes from the mathematical model at the macroscale concerning the drying behavior of microparticles in a tray and in a vial are then presented and can be used for process design. Some further data, with detailed interpretation and discussion of the presented data, can be found in the related research data article, “A multi-scale computational framework for modelling the freeze-drying of microparticles in packed-beds” (Capozzi et al., 2019).

The performance of polymeric ultrafiltration membranes functionalized with polydopamine to couple depth adsorption of contaminants with the typical surface rejection characteristics of the membrane is investigated. Two approaches are deployed to achieve this functionalization: in a two-step method, the ultrafiltration membranes are initially fabricated by phase inversion, then followed by coating with polydopamine; in a more facile and advantageous one-step method, the membranes are subjected to phase inversion in a water solution containing dopamine, so that polymer precipitation and polydopamine functionalization occur at the same time. Methylene blue is used as the representative target contaminant to study the enhancement of membrane adsorption behavior, and its removal is investigated both in batch and under filtration conditions. The sorption capacity increases with increasing polydopamine coating time and is higher for the membranes fabricated via the one-step protocol. The amount of methylene blue adsorbed per unit of membrane mass is large (roughly 5–10 mg g−1) and the kinetics of adsorption is fast. These characteristics allow these materials to get operated effectively and for long times in membrane filtration processes before stopping the system for regeneration. The saturated membranes are completely regenerated and reused without loss of performance by cycling in acidic and alkaline solutions. (Figure presented.).

This paper proposes a systematic work process for the rapid determination of resistance to vapor flow given by the products being freeze-dried. This approach couples mathematical modeling and 3D nondestructive X-ray imaging to reconstruct the internal structure of lyophilized samples. Knowledge of the internal structure is fundamental to better understand the relationship between freezing and within-product heterogeneity as well as between freezing and the drying behavior of the product being lyophilized. The method was validated upon mannitol-based formulations using various freezing protocols. This stepwise approach was demonstrated to be helpful to lyophilization professionals for the control of within-product heterogeneity and for the optimization of the cycle.