Stabilization of proteins in solid form

Immunogenicity of aggregated or otherwise degraded protein delivered from depots or other biopharmaceutical products is an increasing concern, and the ability to deliver stable, active protein is of central importance. We review characterization approaches for solid protein dosage forms with respect...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2015-10, Vol.93, p.14-24
Main Authors: Cicerone, Marcus T., Pikal, Michael J., Qian, Ken K.
Format: Article
Language:English
Subjects:
Aggregation
Chemistry, Pharmaceutical - methods
Delayed-Action Preparations
Drug Delivery Systems
Drug Stability
Dynamic stabilization
Humans
Hydrobromic Acid
Lyophilization
Protein stability
Proteins - administration & dosage
Proteins - chemistry
Proteins - immunology
Water substitution
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Summary:Immunogenicity of aggregated or otherwise degraded protein delivered from depots or other biopharmaceutical products is an increasing concern, and the ability to deliver stable, active protein is of central importance. We review characterization approaches for solid protein dosage forms with respect to metrics that are intended to be predictive of protein stability against aggregation and other degradation processes. Each of these approaches is ultimately motivated by hypothetical connections between protein stability and the material property being measured. We critically evaluate correlations between these properties and stability outcomes, and use these evaluations to revise the currently standing hypotheses. Based on this we provide simple physical principles that are necessary (and possibly sufficient) for generating solid delivery vehicles with stable protein loads. Essentially, proteins should be strongly coupled (typically through H-bonds) to the bulk regions of a phase-homogeneous matrix with suppressed β relaxation. We also provide a framework for reliable characterization of solid protein forms with respect to stability. [Display omitted]
ISSN:0169-409X
1872-8294
DOI:10.1016/j.addr.2015.05.006