Using the Sub-Glass Transition Vibrational Dynamics to Predict Protein Stability in the Solid State: Fact or Fiction?

Maarten Batens; Talia A. Shmool; Jan Massant; J. Axel Zeitler; Guy Van den Mooter

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arXiv · 1911.01732

Using the Sub-Glass Transition Vibrational Dynamics to Predict Protein Stability in the Solid State: Fact or Fiction?

Maarten Batens·Talia A. Shmool·Jan Massant·J. Axel Zeitler·Guy Van den Mooter

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Abstract

The $\beta$-relaxation associated with the sub-glass transition temperature ($T_{\text{g},\beta}$) is attributed to fast, localised molecular motions which can occur below the primary glass transition temperature ($T_{g\alpha}$). Despite $T_{\text{g},\beta}$ being observed well-below storage temperatures, the $\beta$-relaxation associated motions have been hypothesised to influence protein stability in the solid state and could thus impact the quality of, e.g. protein powders for inhalation or reconstitution and injection. However, to date, there is no comprehensive explanation in the literature which answers the question: How is protein stability during storage influenced by the $\beta$-relaxation? Here, we connect the shape of the potential energy surface (PES) to data obtained from our own (storage) stability study, to answer this question. The 52-week stability study was conducted on a selection of multi-component monoclonal antibody (mAb) formulations. Solid state dynamics of the formulations were probed using terahertz time-domain spectroscopy (THz-TDS) and dynamic mechanical analysis (DMA).

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Maarten Batens, Talia A. Shmool, Jan Massant, J. Axel Zeitler, Guy Van den Mooter. 2019-11-05. Using the Sub-Glass Transition Vibrational Dynamics to Predict Protein Stability in the Solid State: Fact or Fiction?. https://arxiv.org/abs/1911.01732

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