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

    Research output: Contribution to journalArticle

    5 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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    Excipients
    Spectrum Analysis
    Monoclonal Antibodies
    Water
    Proline
    Sucrose
    Arginine
    Proteins
    Protein Stability
    Viscosity
    Hot Temperature

    Cite this

    Wallace, Vincent ; Ferachou, D. ; Ke, P. ; Day, K. ; Uddin, S. ; Casas-Finet, J. ; Van Der Walle, C.F. ; Falconer, R.J. ; Zeitler, J.A. / Modulation of the Hydration Water Around Monoclonal Antibodies on Addition of Excipients Detected by Terahertz Time-Domain Spectroscopy. In: Journal of Pharmaceutical Sciences. 2015 ; Vol. 104, No. 12. pp. 4025-4033.
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    abstract = "{\circledC} 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.",
    author = "Vincent Wallace and D. Ferachou and P. Ke and K. Day and S. Uddin and J. Casas-Finet and {Van Der Walle}, C.F. and R.J. Falconer and J.A. Zeitler",
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    Wallace, V, Ferachou, D, Ke, P, Day, K, Uddin, S, Casas-Finet, J, Van Der Walle, CF, Falconer, RJ & Zeitler, JA 2015, 'Modulation of the Hydration Water Around Monoclonal Antibodies on Addition of Excipients Detected by Terahertz Time-Domain Spectroscopy' Journal of Pharmaceutical Sciences, vol. 104, no. 12, pp. 4025-4033. https://doi.org/10.1002/jps.24630

    Modulation of the Hydration Water Around Monoclonal Antibodies on Addition of Excipients Detected by Terahertz Time-Domain Spectroscopy. / Wallace, Vincent; Ferachou, D.; Ke, P.; Day, K.; Uddin, S.; Casas-Finet, J.; Van Der Walle, C.F.; Falconer, R.J.; Zeitler, J.A.

    In: Journal of Pharmaceutical Sciences, Vol. 104, No. 12, 2015, p. 4025-4033.

    Research output: Contribution to journalArticle

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