Surface Tension and Self-association Properties of Aqueous Polysorbate 20 HP and 80 HP Solutions: Insights into Protein
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ORIGINAL ARTICLE
Surface Tension and Self-association Properties of Aqueous Polysorbate 20 HP and 80 HP Solutions: Insights into Protein Stabilisation Mechanisms Patrick Garidel 1
&
Michaela Blech 1 & Julia Buske 1 & Alfred Blume 2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Objective Polysorbates 20 and 80 are the most used surfactants for the development of parenteral protein formulations, because of their beneficial safety and stabilisation profile. Although, showing excellent stabilisation properties, the stabilisation mechanism(s) of these surfactants for aqueous protein formulations are still unclear. Different stabilisation models have been discussed in the literature, among them the possible formation of protein-surfactant micelle complexes. Methods This study focusses on the determination of the self-association properties of compendial grade polysorbate 20 HP (PS 20 HP) and polysorbate 80 HP (PS 80 HP) with regard to the formed micelle size (by dynamic light scattering, DLS), the concentration upon which the surfactant molecules self-associate (cmr, critical micelle concentration range) to form micelles, and the related surface tension. Surface tension and micelle size were determined as a function of temperature, as well as composition of the formulation (presence of a buffer salt and influence of ionic strength). Results The critical micelle concentration range values (cmr) at 25 °C are between 15–75 μM for PS 20 HP, but considerably lower for PS 80 HP with 7–16 μM, depending only slightly on the formulation composition. With increasing temperature, the cmr decreases slightly. PS 80 HP forms larger micelles (Rh = 4.5 nm) compared with PS 20 HP (Rh = 3.5 nm) (25 °C). The temperature dependency of the micelle size is more pronounced for PS 80 HP. Conclusions Based on these results, the suggested stabilisation mechanism, especially for antibody formulations, by the formation of antibody-polysorbate micelle complexes, is critically discussed, and the current study shows that this stabilisation mechanism is not likely, for commonly used monoclonal antibody formulations. Keywords Polysorbate . Tween . Surfacetension . Critical micelle concentration range . Dynamic light scattering . Hydrodynamic size
Introduction Polysorbates, also known under the tradename of Tween, are surface active compounds derived from ethoxylated sorbitan esterified with various fatty acids. Polysorbate 20 is mainly esterified with lauric acid, whereas polysorbate 80 is mainly esterified with oleic acid. According to the specifications
* Patrick Garidel [email protected] 1
Boehringer Ingelheim Pharma GmbH & Co. KG, Innovation Unit, PDB, 88397 Biberach an der Riss, Germany
2
Institute of Chemistry - Physical Chemistry, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany
listed in the pharmacopoeia, polysorbate is composed of 40– 60% of lauric acid, whereas polysorbate 80 contains at least ≥ 58% oleic acid ([1] and references cited therein). Figure 1 illustra
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