Interfacial and self-association behaviour of poloxamer 188 in aqueous solutions

• P188 solutions were investigated by DSC, DLS, surface pressure measurements, fluorescence spectroscopy, EPR and NMR. • The association and interfacial behaviour of P188 is multi-phased and extremely temperature-dependent. • Poloxamer 188 does not form micelles in water at 37 °C and below. • Pharmaceutical excipients like citrate buffer, sodium chloride and trehalose shift the CMC to lower values. Poloxamer 188 plays a vital role as an excipient in the pharmaceutical industry. It is used as a solubiliser, wetting agent, shear protectant and stabiliser in protein and viral vector formulations. In this work, we characterise poloxamer 188s micelle formation characteristics using surface tension measurements to investigate the interfacial behaviour. In addition, differential scanning calorimetry was used to monitor unfolding processes at increasing temperatures. The size of the surfactant association was followed by dynamic light scattering, and fluorescence spectroscopy was used to get insights into the formation of a hydrophobic compartment by poloxamer 188 micelles. Additionally, electron paramagnetic resonance spectroscopy provided information about micro-viscosity and polarity. Nuclear magnetic resonance spectroscopy ( 1 H and 13 C) complemented the set of methods by providing data on the chemical environment of the polymer blocks. Poloxamer 188 concentrations up to 160 mg·mL −1 were investigated at temperatures between 5 °C to 80 °C. A strong dependency on temperature and solutes in surfactant solutions was found, conditional on their influence on the association behaviour in aqueous solution. We conclude that poloxamer 188 does not form micelles under conditions relevant to pharmaceutical formulation as a function of surfactant concentration, temperature and buffer system. The suspected reason for this is the very high hydrophilicity of the poloxamer molecule and the strong temperature dependence of the polyethylene oxide content in particular. Poloxamer 188 becomes increasingly lipophilic to show micelle formation only at increased temperature or in the presence of specific trehalose concentrations. These results provide insight into the characteristics of poloxamer 188 in aqueous solutions, allowing the stabilisation properties of drugs in drug delivery systems to be elucidated.