Characterization of antibody-polyol interactions by static light scattering: implications for physical stability of protein formulations.

In this study, the nature of interactions between monoclonal antibodies and polyols was studied using static light scattering. Solutions of mAb-U and mAb-P (4-12 mg/mL) were analyzed using static light scattering in buffer, 10% w/v trehalose and ethylene glycol solutions at pH 5.0, 7.0 and 9.0. Mechanical stress studies were conducted by shaking the mAb-U solutions (5mg/mL, pH 5.0, 7.0 and 9.0) and mAb-P solutions (5mg/mL, pH 7.0) at 200 rpm for 5 days at 25°C. Addition of trehalose and ethylene glycol resulted in a decrease in the attractive interactions between mAb-U molecules at pH 7.0 and 9.0, and at pH 9.0 between mAb-P molecules. At a higher ionic strength (300 mM, pH 5.0) trehalose and ethylene glycol decreased attractive interactions for both mAbs. Mechanical stress studies showed higher aggregation of mAb-U in trehalose solutions than ethylene glycol and buffer solutions at pH 7.0 and 9.0. A converse trend was seen for mAb-P at pH 7.0. This study showed that polyols, conformational stabilizers or destabilizers, decrease attractive interactions between protein molecules. The decrease is a result of masking of the hydrophobic sites on a protein as polyols can have favorable hydrophobic interactions with the surface exposed hydrophobic groups.