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Alternative Methods of Controlling Nucleation in Freeze Drying

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Lyophilization of Pharmaceuticals and Biologicals

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

The control of freezing, and particularly of the nucleation temperature, is one of the most challenging aspects of the development of a lyophilization cycle. Technological advances of recent years have increased the efficiency with which nucleation temperature can be adjusted. This chapter discusses these technologies, as well as some emerging technologies that might play an important role in near future. In particular each technology is presented in terms of easy to be implemented, scalability on industrial units, influence on product morphology, protein preservation, intra-vial and vial-to-vial heterogeneity, and process performance.

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Abbreviations

HES:

Hydroxyethyl starch

SSA:

Specific surface area

VISF:

Vacuum-induced surface freezing

D p :

Pore size, m

J w :

Vapour flux, kg m−2 s−1

M w :

Molecular weight of water, kg mol−1

P ice :

Vapour pressure of ice, Pa

P w :

Partial pressure of water inside the drying chamber, Pa

R p :

Resistance to mass transfer, m s−1

R :

Ideal gas constant, J mol−1 K−1

Tg′:

Glass transition temperature, K

T eu :

Eutectic temperature, K

T n :

Nucleation temperature, K

ε :

Porosity of the lyophilized product, –

τ :

Tortuosity of the lyophilized product, –

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  1. Department of Applied Science and Technology, Molecular Engineering Laboratory, Politeccnico di Torino, Torino, Italy

    Roberto Pisano

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    Kevin R. Ward

  2. National Institute for Biological Standards & Control (NIBSC), Potters Bar, Hertfordshire, UK

    Paul Matejtschuk

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Pisano, R. (2019). Alternative Methods of Controlling Nucleation in Freeze Drying. In: Ward, K., Matejtschuk, P. (eds) Lyophilization of Pharmaceuticals and Biologicals. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8928-7_4

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  • DOI: https://doi.org/10.1007/978-1-4939-8928-7_4

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8927-0

  • Online ISBN: 978-1-4939-8928-7

  • eBook Packages: Springer Protocols

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