Modulation of the Hydration Water Around Monoclonal Antibodies on Addition of Excipients Detected by Terahertz Time-Domain Spectroscopy

Vincent Wallace, D. Ferachou, P. Ke, K. Day, S. Uddin, J. Casas-Finet, C.F. Van Der Walle, R.J. Falconer, J.A. Zeitler

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    12 Citations (Scopus)

    Abstract

    © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association. Terahertz time-domain spectroscopy (THz-TDS) has been shown to detect overlapping extended hydration layers around proteins. Here, we used THz-TDS to detect modulation of the extended hydration layer around monoclonal antibodies (mAbs) by the introduction of commonly used excipients. Proline and sucrose altered the hydration layer around a mAb (mAb1), which was observed as a negative shift in the plateau in absorbance above μ100 mg/mL mAb1 (μ70,000 water molecules per mAb); arginine had no effect. At lower concentrations of μ10 mg/mL mAb1 (μ700,000 water molecules per mAb) proline and arginine modulated the hydration layer, which was observed as a negative shift in the relative absorbance, whereas sucrose had no effect. The changes in the extended hydration layer were not translated to shifts in the thermal stability or protein:protein interaction parameter. The hydration layer of a second mAb (mAb2) was further shown to be modulated by more complex formulations composed of two or more excipients; although the differences in terahertz absorbance were not predictive of viscosity or long-term stability. THz-TDS promises to be a useful tool for understanding a protein's interaction with excipients in solution and the challenge will be to determine how to apply this knowledge to protein formulation.
    Original languageEnglish
    Pages (from-to)4025-4033
    JournalJournal of Pharmaceutical Sciences
    Volume104
    Issue number12
    DOIs
    Publication statusPublished - 2015

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