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Complex Micellization Behavior of the Polysorbates Tween 20 and Tween 80.
Hannah Knoch1, Maximilian H Ulbrich2,3, Judith J Mittag4
1Institute of Pharmaceutical Sciences, University of Freiburg, 79085 Freiburg im Breisgau, Germany.
Molecular Pharmaceutics
|July 12, 2021
Summary
Polysorbates (PSs) form complex micelles, not simple ones like single surfactants. Their micelle composition and properties change with concentration, differing between PS20 and PS80 grades.
Area of Science:
- Physical Chemistry
- Materials Science
- Pharmaceutical Science
Background:
- Polysorbates (PSs) are crucial non-ionic surfactants in pharmaceuticals, used for stabilizing biologics and solubilizing active ingredients.
- Their complex composition, featuring variable fatty acid and ethylene oxide chain lengths, leads to intricate self-assembly behavior distinct from simple surfactants.
Purpose of the Study:
- To characterize the complex micellization and demicellization behavior of pharmaceutical-grade polysorbates (PS20 and PS80).
- To investigate how varying concentrations and different PS grades influence micelle formation and properties.
Main Methods:
- Utilized isothermal titration calorimetry (ITC) to perform demicellization experiments across a range of PS concentrations.
- Converted ITC data into micellar enthalpy (Qm(c)) as a function of concentration to analyze micelle formation.
Main Results:
- Initial micelles of PS20 and PS80 form at very low concentrations (2 μM and 10 μM, respectively), primarily composed of species with the lowest critical micelle concentration (cmc).
- As concentration increases, other PS species incorporate into micelles sequentially based on their individual cmcs and hydrophilic-lipophilic balance.
- Micellization and property variations continue up to at least 10 mM, indicating that published cmc values may represent specific components rather than overall micelle absence/constancy.
Conclusions:
- The micellar behavior of PS20 and PS80 is complex and concentration-dependent, differing significantly from single-component surfactants.
- Published cmc values for PSs should be interpreted cautiously, as they may reflect the incorporation of major components rather than a complete absence of micelles below or constant micelle properties above these values.
- Substantial differences in micellization enthalpy curves exist between PS20 and PS80, and even among different quality grades of the same PS type.
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