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Mechanical Behavior and Structure of Freeze-Dried Cakes

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Lyophilization of Pharmaceuticals and Biologicals

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

Abstract

Freeze-drying or the lyophilization of biopharmaceuticals is a standard method for product manufacture in order to increase product shelf-life and minimize the tendency of re-constituted products to aggregate. However, the physical and or mechanical stability of freeze-dried cakes can be problematic, which can directly result in financial losses due to unusable or damaged products. Currently, there is very limited systematic knowledge of the relationship between lyophilization process conditions and the cake-specific physical structure, mechanical performance, and stability. This Chapter reviews the detailed mechanical properties and structure of freeze-dried cakes formed from aqueous solutions with concentrations from 1 to 40% w/v of common excipients, mannitol, sucrose, and trehalose in some detail. In addition, the mechanical properties of commercial freeze-dried products as well as effects of moisture content and ingress into freeze-dried cakes are also reported. Both experimentally measured Young’s moduli and yield stress data scale well with reduced cake density, in line with theoretical predictions from classical cellular solids theory. A novel compressive indentation method is reviewed which can accurately determine a cake’s Young’s modulus and yield stress within 1 min, allowing the potential future use of these mechanical cake attributes as Critical Quality Attributes (CQAs).

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Acknowledgments

A.D. acknowledges the support of the EPSRC Centre for Doctoral Training in Emergent Macromolecular Therapies (CDT) at University College London in collaboration with National Institute for Biological Standards and Control (NIBSC, UK). S.H.M.H. acknowledges the financial support of the EPSRC Impact Acceleration Account at Imperial College.

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Authors and Affiliations

  1. Surfaces and Particle Engineering Group, Department of Chemical Engineering, Imperial College London, London, UK

    Sarah H. M. Hedberg, Sharmila Devi, Arnold Duralliu & Daryl R. Williams

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  1. Sarah H. M. Hedberg
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  2. Sharmila Devi
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  3. Arnold Duralliu
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  4. Daryl R. Williams
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Correspondence to Daryl R. Williams .

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Editors and Affiliations

  1. Biopharma Process Systems Ltd., Winchester, UK

    Kevin R. Ward

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

    Paul Matejtschuk

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Hedberg, S.H.M., Devi, S., Duralliu, A., Williams, D.R. (2019). Mechanical Behavior and Structure of Freeze-Dried Cakes. 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_13

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  • DOI: https://doi.org/10.1007/978-1-4939-8928-7_13

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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

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