Degradation of polysorbates 20 and 80 catalysed by histidine chloride buffer

Abstract

Polysorbates are amphiphilic, non-ionic surfactants, and they represent one of the key components of biopharmaceuticals. They serve as stabilisers, and their degradation can cause particle formation, which has been an industry-wide issue over the past decade. To determine the influence of the buffers most frequently used in biopharmaceuticals on polysorbate degradation, an accelerated stability study was carried out using placebo formulations containing 0.02% polysorbates and 20 mM buffers (pH 5.5, 6.5). These included histidine chloride, sodium citrate, sodium succinate and sodium phosphate buffers. The rate of polysorbate degradation was highest in histidine chloride buffer, and therefore we further focused on the mechanism here. The predominant degradation pathway of polysorbates in this buffer was ester hydrolysis, catalysed by the imidazole moiety of the histidine. Interestingly, the presence of therapeutic proteins in the formulations slowed histidine-catalysed degradation of polysorbates in 50% of cases, with negligible degradation seen otherwise. This emphasises the complex nature of the interactions between the components of biopharmaceutical drug products. Nonetheless, there are disadvantages of using histidine chloride buffers in biopharmaceuticals that contain polysorbates. Careful consideration should be given to selection of excipients used in parenteral formulations, whereby compatibility between buffer and surfactant is of key importance.

Keywords: Biopharmaceutical formulations; Degradation; Histidine buffer; Liquid chromatography; Mass spectrometry; Polysorbates.