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Flow Activation Energy of High-Concentration Monoclonal Antibody Solutions and Protein–Protein Interactions Influenced by NaCl and Sucrose
- Source :
- Molecular Pharmaceutics; September 2024, Vol. 21 Issue: 9 p4553-4564, 12p
- Publication Year :
- 2024
-
Abstract
- The solution viscosity and protein–protein interactions (PPIs) as a function of temperature (4–40 °C) were measured at a series of protein concentrations for a monoclonal antibody (mAb) with different formulation conditions, which include NaCl and sucrose. The flow activation energy (Eη) was extracted from the temperature dependence of solution viscosity using the Arrhenius equation. PPIs were quantified via the protein diffusion interaction parameter (kD) measured by dynamic light scattering, together with the osmotic second virial coefficient and the structure factor obtained through small-angle X-ray scattering. Both viscosity and PPIs were found to vary with the formulation conditions. Adding NaCl introduces an attractive interaction but leads to a significant reduction in the viscosity. However, adding sucrose enhances an overall repulsive effect and leads to a slight decrease in viscosity. Thus, the averaged (attractive or repulsive) PPI information is not a good indicator of viscosity at high protein concentrations for the mAb studied here. Instead, a correlation based on the temperature dependence of viscosity (i.e., Eη) and the temperature sensitivity in PPIs was observed for this specific mAb. When kDis more sensitive to the temperature variation, it corresponds to a larger value of Eηand thus a higher viscosity in concentrated protein solutions. When kDis less sensitive to temperature change, it corresponds to a smaller value of Eηand thus a lower viscosity at high protein concentrations. Rather than the absolute value of PPIs at a given temperature, our results show that the temperature sensitivity of PPIs may be a more useful metric for predicting issues with high viscosity of concentrated solutions. In addition, we also demonstrate that caution is required in choosing a proper protein concentration range to extract kD. In some excipient conditions studied here, the appropriate protein concentration range needs to be less than 4 mg/mL, remarkably lower than the typical concentration range used in the literature.
Details
- Language :
- English
- ISSN :
- 15438384 and 15438392
- Volume :
- 21
- Issue :
- 9
- Database :
- Supplemental Index
- Journal :
- Molecular Pharmaceutics
- Publication Type :
- Periodical
- Accession number :
- ejs67191420
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.4c00460