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How sugars protect proteins in the solid state and during drying (review): Mechanisms of stabilization in relation to stress conditions

Mensink, M. A., Frijlink, H. W., Maarschalk, K. V. D. V. & Hinrichs, W. L. J. May-2017 In : European Journal of Pharmaceutics and Biopharmaceutics. 114, p. 288-295 8 p.

Research output: Scientific - peer-reviewLiterature review

This review aims to provide an overview of current knowledge on stabilization of proteins by sugars in the solid state in relation to stress conditions commonly encountered during drying and storage. First protein degradation mechanisms in the solid state (i.e. physical and chemical degradation routes) and traditional theories regarding protein stabilization (vitrification and water replacement hypotheses) will be briefly discussed. Secondly, refinements to these theories, such as theories focusing on local mobility and protein-sugar packing density, are reviewed in relationship to the traditional theories and their analogies are discussed. The last section relates these mechanistic insights to the stress conditions against which these sugars are used to provide protection (i.e. drying, temperature, and moisture). In summary sugars should be able to adequately form interactions with the protein during drying, thereby maintaining it in its native conformation and reducing both local and global mobility during storage. Generally smaller sugars (disaccharides) are better at forming these interactions and reducing local mobility as they are less inhibited by steric hindrance, whilst larger sugars can reduce global mobility more efficiently. The principles outlined here can aid in choosing a suitable sugar as stabilizer depending on the protein, formulation and storage condition-specific dominant route of degradation. (C) 2017 The Authors. Published by Elsevier B.V.

Original languageEnglish
Pages (from-to)288-295
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume114
StatePublished - May-2017

Keywords

  • Biologicals, Storage stability, Temperature, Water activity, Vitrification, Mobility, Degradation, MINI FREEZE-DRYER, STORAGE STABILITY, CHEMICAL-STABILITY, LACTATE-DEHYDROGENASE, LYOPHILIZED FORMULATIONS, INFRARED-SPECTROSCOPY, THERAPEUTIC PROTEINS, DRIED PROTEINS, AGGREGATION, GLASSES

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