Polysorbates are an important class of amphipathic, nonionic surfactants that are widely used in the pharmaceutical industry. They are used both clinically and preclinically, due to their effectiveness at low concentrations and relatively low toxicities (1-2). In the formulation of proteins, they are used as surfactants to prevent surface absorption, limiting physical damage during purification, filtration, transportation, freeze-drying, storage and delivery (3). Polysorbate 20 (PS 20 – polyoxyethylene sorbitan.

(PS 80 – polyoxyethylene sorbitan monooleate) are the most common polysorbates used in the formulation of protein biopharmaceuticals. They are composed of diverse mixtures of different fatty acid esters and the solutions sold by the manufacturers are labeled either as polysorbate 20 or 80 or under the trade names Tween® 20 and Tween® 80. 

The Idea

It is known that polysorbates are prone to degradation by autoxidation. This article provides an example of a free radical chain reaction that leads to polysorbate degradation. It starts with the oxidation of fatty acid esters, either by metal-, temperature- or light-induced processes to form various fatty acid free radicals. These free radicals are usually carbon centered and react rapidly with oxygen to form alkylperoxyl radicals. Alkylperoxyl radicals promote further free radical formation by abstracting hydrogen atoms from other fatty acid ester molecules. The alkylperoxyl radicals are converted to hydroperoxides that either undergo thermolysis or react with metals to form alkoxyl, alkylperoxyl and carbon centered free radicals. This free radical chain reaction proceeds until it is terminated.

Kalina Ranguelova, 2018