Advancing predictions of protein stability in the solid state.

Area of Science:

• Physical Chemistry
• Biophysics
• Materials Science

Background:

• The β-relaxation, linked to molecular motions below the glass transition temperature (T_g,β), is hypothesized to influence the stability of proteins in solid formulations.
• Understanding these dynamics is crucial for maintaining the quality of protein-based products like powders for inhalation or injection.

Purpose of the Study:

• To explore the relaxation dynamics in glassy solid-state monoclonal antibody formulations.
• To investigate the reliability of T_g,β as a parameter for characterizing solid-state protein behavior.
• To develop an approach for analyzing solid-state dynamics and their relationship to protein stability over prolonged storage.

Main Methods:

• Terahertz time-domain spectroscopy (THz-TDS).
• Dynamical mechanical analysis (DMA).
• A 52-week stability study of multi-component spray-dried formulations.

Main Results:

• Distinct solid-state protein formulations exhibit different stability profiles after prolonged storage, despite similar initial aggregation.
• The study outlines a method to characterize solid-state dynamics and their correlation with protein stability.

Conclusions:

• The β-relaxation dynamics are critical for understanding long-term protein stability in solid formulations.
• The proposed analytical approach can characterize solid-state dynamics and their impact on protein quality over time.