Micellar Morphology of Polysorbate 20 and 80 and Their Ester Fractions in Solution via Small-Angle Neutron Scattering

Surfactants are commonly used in therapeutic protein formulations in biopharmaceuticals to impart protein stability; however, their solution morphology and the role of the individual components in these structurally heterogeneous commercial grade surfactants at physiologically and pharmaceutically relevant temperatures have not been investigated systematically. The micellar morphologies of Polysorbate 20 and Polysorbate 80 and their primary components monoester fractions, as well as the diester fractions, are evaluated at 4, 22 degrees C, 40 degrees C, and 50 degrees C using small-angle neutron scattering to determine the aggregation number, radius of gyration, core radius, critical micelle concentration, shell thickness, and shell hydration. The sizes and aggregation numbers of the diester fractions of PS20 above 80 degrees C and PS80 above 50 degrees C exhibit significant changes in shape. The analysis of the small-angle neutron scattering data of PS20 confirms that the critical micellar concentration of the monoester fraction is significantly higher at 4 degrees C compared to the diester fraction and their original material, all-laurate PS20. Overall, these experiments identify the dominant components responsible for the temperature-dependent behavior of these surfactants in pharmaceutical protein formulations. (C) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.