Preservative Induced Polysorbate 80 Micelle Aggregation

Published

June 1, 2021

Author(s)

Peter H. Gilbert, Zhenhuan Zhang, Ken K. Qian, David P. Allen, Norman J. Wagner, Yun Liu

Abstract

Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology. This slow preservative-induced destabilization of PS80 micelles progresses over days or even weeks, which highlights the essential role that micelle growth kinetics plays in preservative-surfactant interactions. The temperature-dependence of PS80 micelle growth kinetics is quantified by SANS in the presence of m-cresol. The monotonic growth of aggregate size with time follows a power-law, providing evidence for the mechanism. Addition of a pH-regulating citrate buffer accelerates micelle aggregation kinetics.

Citation

Journal of Pharmaceutical Sciences

Volume

110

Issue

6

Pub Type

Journals

Keywords

micelles, small-angle neutron scattering, polysorbate, preservatives, pharmaceutical formulation

Citation

Gilbert, P. , Zhang, Z. , Qian, K. , Allen, D. , Wagner, N. and Liu, Y. (2021), Preservative Induced Polysorbate 80 Micelle Aggregation, Journal of Pharmaceutical Sciences (Accessed May 7, 2025)