Skip to main content

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 59))

  • 997 Accesses

Abstract

Dynamic spray freeze drying combines spray freezing and rotary freeze drying to generate homogeneous, free-flowing lyophilized beads as a bulk intermediate product. This allows for filling on demand, with choices in dose strength and combinations of multiple active materials. Thus, the supply chain becomes highly flexible. This feature of handling bulk intermediate can significantly reduce time to market.

Production efficiency is enabled by using higher concentrated liquids yet maintaining fast reconstitution. Further processing with established solid dosage form technologies is possible, for example film coating for light or oxygen protection in diagnostic applications. The technology is built and tested in lab, pilot and production scale including its use for the manufacture of parenteral products, which is done in a fully contained process line. Industrial uses of the technology are in the areas of pharmaceuticals, diagnostics and medical devices, and specialty chemicals applications.

Note: All figures, and tables are courtesy of Meridion Technologies GmbH of Muellheim Germany. Figure 2 is also courtesy of Credence MedSystems Inc. of Menlo Park California USA.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Jaberidoost M, Nikfar S, Abdollahiasl A, Dinarvand R. Pharmaceutical supply chain risks: a systematic review. DARU J Pharm Sci. 2013;21:69. https://link.springer.com/article/10.1186/2008-2231-21-69. Accessed 16 Dec 2021.

    Article  Google Scholar 

  2. Ezsak R. Addressing the elephant in the pharma supply chain. Pharma Manufacturing. 2021. https://www.pharmamanufacturing.com/articles/2021/addressing-the-elephant-in-the-pharma-supply-chain/. Accessed 16 Dec 2021.

  3. Mesa-Vieira C, Botero-Rodriguez F, Padilla-Munoz A, Franco OH, Gomez-Restrepo C. The dark side of the moon: global challenges in the distribution of vaccines and implementation of vaccination plans against COVID-19. Maturitas. 2021;150:61–3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279820/#. Accessed 16 Dec 2021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. AbdoulFotouh K, Cui Z, Williams RO. Next-generation COVID-10 vaccines should take efficiency of distribution into consideration. APPS PharmSciTech. 2021;22(3):126. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034273/. Accessed 16 Dec 2021.

    Article  Google Scholar 

  5. Fissore D. Freeze-drying in the coffee industry. New Food. https://www.newfoodmagazine.com/article/16968/freeze-drying-in-the-coffee-industry/. Accessed 16 Dec 2021.

  6. Bhatta S, Stevanovic Janezic T, Ratt C. Freeze-drying of plant-based foods. Foods. 2020;9(1):87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022747/. Accessed 16 Dec 2021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Butreddy A, Dudhipala N, Janga KY, Gaddam PR. Lyophilization of small-molecule injectables: and industry perspective on formulation development, process optimization, scale-up challenges and drug product quality attributes. AAPS PharmSciTech. 2020;21:52.

    Article  Google Scholar 

  8. Challener C. For lyophilization excipients really do matter. Biopharm Int. 2017;30(1):32–5.

    Google Scholar 

  9. Nugraheni RW, Mulyadi NA, Yusuf H. Freeze-dried liposome formulation for small molecules, nuceleic acid and protein delivery. Sys Rev Pharm. 2020;11(7):143–51. https://www.sysrevpharm.org/articles/freezedried-liposome-formulation-for-small-molecules-nucleic-acid-and-protein-delivery.pdf. Accessed 16 Dec 2021.

    CAS  Google Scholar 

  10. Meryman HT. Historical recollections of freeze-drying. Dev Biol Stand. 1976;36:29–32.

    CAS  PubMed  Google Scholar 

  11. Da Silva Neves A, Luna AS, Augusto da Costa AC. Optimization of a freeze-drying cycle of a viral vaccine based on changes in temperature, time and geometry of the vials. J Appl Pharm Sci. 2015;5(2):022–9.

    Article  Google Scholar 

  12. Wallen AJ, VanOcker SH, Sinacola JR, Phillips BR. The effect of loading process on product collapse during large-scale lyophilization. J Pharm Sci. 2009;98:997–1004.

    Article  CAS  PubMed  Google Scholar 

  13. Pikal MJ, Cardon S, Bhugra C, Jameel F, Rambhatla S, Mascarenhas WJ, Akay HU. The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications. Pharm Dev Technol. 2005;10(1):17–32.

    Article  CAS  PubMed  Google Scholar 

  14. Trappler EH. Assure batch uniformity for freeze-dried products. Pharm Manufacturing. 2005, March. https://www.pharmamanufacturing.com/articles/2005/191/. Accessed 27 July 2018.

  15. Ganguly A, Varma N, Sane P, Bogner R, Pikal M, Alexeenko A. Spatial variation of pressure in the lyophilization product chamber Part1: computational Modeling. AAPS PharmSciTech. 2017;18(3):577–85.

    Article  PubMed  Google Scholar 

  16. Khan M, Jameel F. Quality-by-design as applied to the development and manufacturing of a lyophilized protein product. Am Pharm Rev. 2009, December. www.americanpharmaceuticalreview.com/Featured-Articles/117782-Quality-by-Design-as-Applied-to-the-Development-and-Manufacturing-of-a-Lyophilized-Protein-Product/. Accessed 28 July 2018.

  17. Merkuryeva G, Valberga A, Smirnov A. Demand forecasting in pharmaceutical supply chains: a case study. Procedia Comput Sci. 2019;149:3–10.

    Article  Google Scholar 

  18. Amoro E, Vanmackere K, White MA. Apparatus and method for cryogranulating a pharmaceutical composition. United States Patent 859-32-B2. 2013.

    Google Scholar 

  19. Thakkar SG, Ruwona TB, Williams RO, Cui Z. The immunogenicity of thin-film freeze dried, aluminum salt-adjuvanted vaccine when exposed to different temperatures. Hum Vaccin Immunother. 2017;13(4):936–46.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang J-L, Hanafy MS, Xu H, Leal J, Zhai Y, Gosh D, Williams RO, Cui Z. Aerosolizable Si RNA-encapsulated solid lipid nanoparticles prepared by thin-film freeze-drying for potential pulmonary delivery. Int J Pharm. 2021;596:120215.

    Article  CAS  PubMed  Google Scholar 

  21. Kahn AH. Kaltlufttrocknung von pharmazeutischen Präparaten und von gefrorenen Lösungen in der Wirbelschicht; PhD thesis, Basle University (CH). 1987.

    Google Scholar 

  22. Mumenthaler M, Leuenberger H. Atmospheric spray-freeze drying: a suitable alternative in freeze-drying technology. Int J Pharm. 1991;72(2):97–110.

    Article  CAS  Google Scholar 

  23. Plitzko M. Gefriertrocknung in der Wirbelschicht; PhD thesis, Basle University (CH). 2006.

    Google Scholar 

  24. Leuenberger H, Plitzko M, Puchkov M. Spray freeze drying in a fluidized bed at normal and low pressure. Dry Technol. 2006;24(6):711–9.

    Article  CAS  Google Scholar 

  25. Suverkrup R, Eggerstedt S, Wanning S, Kuschel M, Sommerfield M, Lamprecht A. Collisions and coalesence in droplet streams for the production of freeze-dried powders. Colloids Surf B: Biointerfaces. 2016;141:443–9.

    Article  PubMed  Google Scholar 

  26. Adali MB, Baressi A, Boccardo G, Pisano R. Spray freeze-drying as a solution to continuous manufacturing of pharmaceutical products in bulk. PRO. 2020;8:709.

    CAS  Google Scholar 

  27. Lowe D, Mehta M, Govindan G, Gupta K. Spray freeze-drying technology: enabling flexibility of supply chain and drug-product presentation for biologics. Bioprocess Int. 2018, December. https://bioprocessintl.com/manufacturing/supply-chain/spray-freeze-drying-technology-enabling-flexibility-of-supply-chain-and-drug-product-presentation-for-biologics/. Accessed 30 Jan 2022.

  28. Luy B, Plitzko M, Struschka M. Process line for the production of freeze-dried particles. US patent 20140245629A1. 2014.

    Google Scholar 

  29. Brandenberger HR, Widmer F. Immobilization of highly concentrated cell suspensions using the laminar jet breakup technique. Biotechnol Prog. 1999;15(3):366–72.

    Article  CAS  PubMed  Google Scholar 

  30. Sebastiao IB, Robinson TD, Alexeenko A. Atmospheric spray freeze-drying: numerical modeling and comparison with experimental measurements. J Pharm Sci. 2017;106(1):183–92.

    Article  Google Scholar 

  31. Sebastiao IB, Bhatnagar B, Tchessalov S, Ohtake S, Plitzko M, Luy B, Alexeenko A. Bulk dynamic freeze-drying part 1: model-based parametric study for spray-freezing process characterization. J Pharm Sci. 2019;108:2063–74.

    Article  CAS  PubMed  Google Scholar 

  32. Sebastiao IB, Bhatnagar B, Tchessalov S, Ohtake S, Plitzko M, Luy B, Alexeenko A. Bulk dynamic freeze-drying part 2: model-based parametric study for spray-freezing process characterization. J Pharm Sci. 2019;108:2075–85.

    Article  CAS  PubMed  Google Scholar 

  33. Meister E, Gieseler H. A significant comparison between the collapse and glass transition temperatures. Eur Pharm Rev. 2008. https://www.europeanpharmaceuticalreview.com/article/1479/a-significant-comparison-between-collapse-and-glass-transition-temperatures/. Accessed 16 Dec 2021.

  34. Ehlers S, Schroeder R, Friess W. Trouble with the neighbor during freeze-drying: rivalry about energy. J Pharm Sci. 2021;110(3):1219–26.

    Article  CAS  PubMed  Google Scholar 

  35. Jameel F, Alexeenko A, Bhambhani A, Sacha G, Zhu T, Tchessalov S, Kumar L, Sharma P, Moussa E, Iyer L, Fang R, Srinivasan J, Tharp T, Azzarella J, Kazarin P, Jalal M. Recommended best practices for lyophilization validation – 2021 part I: process design and modeling. AAPS PharmSciTech. 2021;22(7):221.

    Article  PubMed  Google Scholar 

  36. Jameel F, Alexeenko A, Bhambhani A, Sacha G, Zhu T, Tchessalov S, Kumar L, Sharma P, Moussa E, Iyer L, Luthra S, Srinivasan J, Tharp T, Azzarella J, Kazarin P, Jalal M. Recommended best practices for lyophilization validation – 2021 part II: process qualification and continued process verification. AAPS PharmSciTech. 2021;22(8):266.

    Article  PubMed  Google Scholar 

  37. Pikal MJ, Mascarenhas WJ, Akay HU, Cardon S, Bhugra C, Jameel F, Rambahatla S. The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications. Pharm Dev Technol. 2005;10(1):17–32.

    Article  CAS  PubMed  Google Scholar 

  38. Baker JC. Deputy Director, Office of Biotechnology Products, CDER at FDA; statement during FDA & NAS workshop on continuous manufacturing for the modernization of pharmaceutical production; Washington D.C., July 2018.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bernhard Luy .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 America Association of Pharmaceutical Scientists

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Luy, B., Plitzko, M., Stamato, H. (2023). Design and Process Considerations in Spray Freeze Drying. In: Jameel, F. (eds) Principles and Practices of Lyophilization in Product Development and Manufacturing . AAPS Advances in the Pharmaceutical Sciences Series, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-031-12634-5_14

Download citation

Publish with us

Policies and ethics