Spray Freeze-Drying as a Solution to Continuous Manufacturing of Pharmaceutical Products in Bulk

Abstract

Pharmaceutical manufacturing is evolving from traditional batch processes to continuous ones. The new global competition focused on throughput and quality of drug products is certainly the driving force behind this transition which, thus, represents the new challenge of pharmaceutical manufacturing and hence of lyophilization as a downstream operation. In this direction, the present review deals with the most recent technologies, based on spray freeze-drying, that can achieve this objective. It provides a comprehensive overview of the physics behind this process and of the most recent equipment design.

The Freeze-Drying of Foods—The Characteristic of the Process Course and the Effect of Its Parameters on the Physical Properties of Food Materials

“…Cellular materials have a certain porosity that positively influences mass transport resistance [ 27 ]. In the case of frozen liquids, it is possible to create a porous structure of the material and reduce the heat and mass transport path via the application of the new spray-freezing into liquid (SFL) technology [ 28 , 29 , 30 , 31 , 32 , 33 ]. By spraying the liquid into liquid nitrogen or cold air, it is possible to obtain a material in the form of ice spheres and thus obtain a porous bed that is then freeze-dried.…”

Economic Analysis of a Freeze-Drying Cycle

“…The model presented in this work provides the industry with a methodological approach to determine a priori the eventual economic convenience of cycle optimization. Furthermore, in the last decade, great efforts have been made in the development of new technologies regarding continuous freeze-drying [19][20][21] and economic comparisons are required for the preliminary feasibility studies. This model is indeed suitable for such analysis.…”

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

“…Solvent sublimation of atomized particles has often led to the formation of spherical, porous particles with low density, which promotes aerosolization [ 9 ]. Furthermore, recent developments in SFD technology have allowed production scale-up and continuous manufacture to become possible [ 5 , 24 ], making it a feasible method to manufacture protein therapeutics on an industrial scale. However, our understanding of SFD is still rather limited compared to other drying methods, such as SD and freeze-drying, partially due to its rather diverse approach in producing dry powder.…”

“…However, it also suffers from disadvantages, such as high-temperature exposure with relatively low production yield [ 4 ]. Spray-freeze-drying (SFD) is another particle engineering technique that has become increasingly popular in producing dry powders for pulmonary delivery of a wide range of therapeutic molecules, including biologics and macromolecules such as proteins, bacteriophages, and nucleic acids [ 5 , 6 , 7 , 8 , 9 ]. Unlike SD, no heating is required for the dehydration process in SFD.…”