Abstract
Tween (polysorbate) 20 and 80 are surfactants used for the development of parenteral protein drugs, due to their beneficial safety profile and stabilisation properties. To elucidate the mechanism by which Tween 20 and 80 stabilise proteins in aqueous solutions, either by a “direct” protein to surfactant interaction and/or by an interaction with the protein film at the air–water interface, we used spectroscopic (Infrared Reflection Absorption Spectroscopy, IRRAS) and microscopic techniques (Brewster Angle Microscopy, BAM) in combination with surface pressure measurements. To this end, the impact of both types of Tweens with regard to the displacement of the protein from the air–water interface was studied. As a model protein, human serum albumin (HSA) was used. The results for the displacement of the adsorbed HSA films by Tweens 20 and 80 can partially be understood on the basis of an orogenic displacement mechanism, which depends on the critical surface pressure of the adsorbed protein film. With increasing concentration of Tween in the sub-phase, BAM images showed the formation of different domain morphologies. IRRA-spectra supported the finding that at high protein concentration in the sub-phase, the protein film could not be completely displaced by the surfactants. Comparing the impact of both surfactants, we found that Tween 20 adsorbed faster to the protein film than Tween 80. The adsorption kinetics of both Tweens and the speed of protein displacement increased with rising surfactant concentration. Tween 80 reached significant lower surface pressures than Tween 20, which led to an incomplete displacement of the observed HSA film.
Highlights
Tweens are non-ionic surfactants which are widely used as co-solutes in various industrial applications, for example in the food industry as emulsifiers, or in pharmaceutical science to stabilise proteins
Re-adsorption of the protein is inhibited due to the adsorbed surfactant layer. We investigate whether this orogenic displacement is a generic mechanism beyond the application to food proteins, i.e. is valid for parenteral protein drug formulations containing Tweens, as in our former studies human serum albumin (HSA) was used as a model protein (Garidel et al 2009; Hoffmann et al 2009)
We first were interested in the question whether a protein film formed at the air water interface of a protein solution could be displaced by the addition of a surfactant, which is surface active
Summary
Tweens are non-ionic surfactants which are widely used as co-solutes in various industrial applications, for example in the food industry as emulsifiers, or in pharmaceutical science to stabilise proteins. The Tweens are polyoxyethylene-1,4-sorbitan-monoesters containing a mixture of fatty acids (Dwivedi et al 2018, 2020). The used and commercially available Tween 20 and 80 are, a mixture of molecules related to the parent molecule sorbitan polyoxyethylene fatty acid ester (Fig. 1). According to the EU specifications, Tween 20 is composed of approx. 14–25% of myristic acid, whereas Tween 80 is composed of ≥ 58% oleic acid (Khan et al 2015). Substantial amounts of polyoxyethylene, sorbitan polyoxyethylene, and isosorbide polyoxyethylene fatty acid mono, di-, tri- and tetra-esters are present (Dwivedi et al 2020)
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