Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: Structure and degradation pathways

被引:578
作者
Kerwin, Bruce A. [1 ]
机构
[1] Amgen Inc, Dept Pharmaceut, Thousand Oaks, CA 91320 USA
关键词
polysorbate; Tween; surfactants; stability; degradation; micelle; proteins; protein formulation; excipients;
D O I
10.1002/jps.21190
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Polysorbates 20 and 80 (Tween(R) 20 and Tween(R) 80) are used in the formulation of biotherapeutic products for both preventing surface adsorption and as stabilizers against protein aggregation. The polysorbates are amphipathic, nonionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan being polyoxyethylene sorbitan monolaurate for polysorbate 20 and polyoxyethylene sorbitan monooleate for polysorbate 80. The polysorbates used in the formulation of biopharmaceuticals are mixtures of different fatty acid esters with the monolaurate fraction of polysorbate 20 making up only 40-60% of the mixture and the monooleate fraction of polysorbate 80 making up >58% of the mixture. The polysorbates undergo autooxidation, cleavage at the ethylene oxide subunits and hydrolysis of the fatty acid ester bond. Autooxidation results in hydroperoxide formation, side-chain cleavage and eventually formation of short chain acids such as formic acid all of which could influence the stability of a biopharmaceutical product. Oxidation of the fatty acid moiety while well described in the literature has not been specifically investigated for polysorbate. This review focuses on the chemical structure of the polysorbates, factors influencing micelle formation and factors and excipients influencing stability and degradation of the polyoxyethylene and fatty acid ester linkages. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.
引用
收藏
页码:2924 / 2935
页数:12
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