A Comprehensive Review of the Latest Trends in Spray Freeze Drying and Comparative Insights with Conventional Technologies

Abstract

Spray freeze drying (SFD) represents an emerging drying technique designed to produce a wide range of pharmaceuticals, foods, and active components with high quality and enhanced stability due to their unique structural characteristics. This method combines the advantages of the well-established techniques of freeze drying (FD) and spray drying (SD) while overcoming their challenges related to high process temperatures and durations. This is why SFD has experienced steady growth in recent years regarding not only the research interest, which is reflected by the increasing number of literature articles, but most importantly, the expanded market adoption, particularly in the pharmaceutical sector. Despite its potential, the high initial investment costs and complex operational requirements may hinder its growth. This paper provides a comprehensive review of the SFD technology, highlighting its advantages over conventional drying techniques and presenting its latest applications focused on pharmaceuticals. It also offers a thorough examination of the principles and the various parameters influencing the process for a better understanding and optimization of the process according to the needs of the final product. Finally, the current limitations of SFD are discussed, and future directions for addressing the economic and technical barriers are provided so that SFD can be widely industrialized, unlocking its full potential for diverse applications.

Keywords: atomization; encapsulation; freeze drying; freezing; pharmaceuticals; spray drying; sublimation.

Figure 1

(a) Number of publications working on the technology of SFD during the last 20 years and (b) subject areas of SFD, according to Scopus data.

Figure 2

Illustrations of the SFD process and the sub-processes of atomization, freezing, and drying (sublimation).

Figure 3

Configurations of (a) two-fluid atomization nozzle, (b) hydraulic atomizer [26] (reproduced with permission from Ohtake et al., copyright John Wiley and Sons).

Figure 4

Freezing configurations: (a) spray freezing into vapor, (b) spray freezing into vapor over liquid, and (c) spray freezing into liquid.

Figure 5

Configurations of (a) fine-SFD system [5], (b) dynamic FD [5], and (c) Rey’s concept.

Figure 6

Powder morphology of (i) spray-freeze-dried at (a) at 500× and (b) 1500× magnitude, (ii) spray-dried at (c) at 500× and (d) 1500× magnitude and (iii) freeze-dried at (e) at 500× and (f) 1500× magnitude micellar casein [90] (reproduced with permission from Ren et al. copyright Elsevier).