Complex Micellization Behavior of the Polysorbates Tween 20 and Tween 80

Abstract

Polysorbates (PSs, Tweens) are widely used surfactant products consisting of a sorbitan ring connecting up to four ethylene oxide (EO) chains of variable lengths, one or more of which are esterified with fatty acids of variable lengths and saturation degrees. Pharmaceutical applications include the stabilization of biologicals in solutions and the solubilization of poorly water soluble, active ingredients. This study characterizes the complex association behavior of compendial PSs PS20 and PS80, which is fundamentally different from that of single-component surfactants. To this end, a series of demicellization experiments of isothermal titration calorimetry with different PS concentrations are evaluated. Their experiment-dependent heats of titration are converted into a common function of the state of a sample, the micellar enthalpy Q m(c). These functions demonstrate that initial micelles are already present at the lowest concentrations investigated, 2 μM for PS20 and 10 μM for PS80. Initial micelles consist primarily of the surfactant species with the lowest individual critical micelle concentration (cmc). With increasing concentration, the other PS species gradually enter these micelles in the sequence of increasing individual cmc’s and hydrophilic–lipophilic balance. Concentration ranges with pronounced slopes of Q m(c) can be tentatively assigned to the uptake of the major components of the PS products. Micellization and the variation of the micelle properties progress up to at least 10 mM PS. That means the published cmc values or ranges of PS20 and PS80 may be related to certain, major components being incorporated into and forming specific micelles but must not be interpreted in terms of an absence of micelles below and constant properties, e.g., the surface activity, of the micelles above these ranges. The micellization enthalpy curves differ quite substantially between PS20 and PS80 and, in a subtler fashion, between individual quality grades such as high purity, pure lauric acid/pure oleic acid, super-refined, and China grade.

Characterization of radicals in polysorbate 80 using electron paramagnetic resonance (EPR) spectroscopy and spin trapping

“…In the case of PS80, this relates to a fraction of oleic acid (18:1) for CG and AO of larger than 99% compared to about 87% for SR and 75% for HP qualities. An overview of the different composition features of these quality grades can be found in Knoch et al ( Knoch et al, 2021 ), Yang et al 15, ( Yang et al, 2021 ) and Table S1. The heterogeneity of commercially available PS seems to be a double-edged matter.…”

Tween-20 induces the structural remodelling of single lipid vesicles

“…The solubilization of the membrane by Tween-20 becomes more prevalent at higher temperatures, as revealed by the shift of the half maximal concentration of the FRET efficiency to lower concentrations at increasing temperatures. Following our previous approach, we quantified this by curve-fitting the Hill model(23) to the data, which yielded a half maximal concentration of 0.11 ± 0.01 mM at 4 °C, ∼0.04-0.06 mM at 21 °C (similar to the reported cmc (34)) and 0.03 ± 0.01 mM at 37 °C. The Hill coefficient was 4.1 ± 0.9 and independent of the temperature.…”

Development of Optimal Composition Formulation of Resveratrol and Solubilisers

“…Поэтому наиболее подходящим методом является растворение RSV и солюбилизатора в интересующем соотношении в общем растворителе с последующим его удалением. В качестве наиболее подходящих растворителей выступают спирты, в которых растворим RSV и легкорастворимы полоксамеры и полисорбаты [14,15]. Однако в них практически не растворимы немодифицированные ЦД [16], тогда как ные растворимы умеренно [17].…”