Synergistic and antagonistic effects of non-ionic surfactants with bile salt + phospholipid mixed micelles on the solubility of poorly water-soluble drugs

Andrew J. Clulow, Bryce Barber, Malinda Salim, Tim Ryan, Ben J. Boyd

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19 Citations (Scopus)


The nature of the interaction of bile salt micelles with exogenous surfactants used in formulations and the consequent impact on drug solubilisation is not well understood. It is often assumed that addition of any surfactant will lead to an enhanced solubility of drug, which is often true in water alone. In this study we have investigated the interaction of a range of typical non-ionic formulation surfactants (Kolliphor EL, Vitamin E TPGS and a range of Pluronics) with bile salt + phospholipid (BS + PL) mixed micelles using small angle X-ray scattering. The solubility of the model poorly water-soluble drug fenofibrate was determined in the mixed micelles and compared to solubility in the presence of increasing exogenous surfactant alone. It was found that while Pluronic F68 did not appear to interact with bile salt micelles and did not impact on the solubility of the drug in the BS + PL micellar system, addition of hydrophobic surfactants led to a synergistic boost in drug solubility, while addition of more hydrophilic surfactants led to a net reduction in drug solubility. With the exception of Pluronic F68, both hydrophobic and hydrophilic surfactants swelled the bile salt mixed micelles leading to the conclusion that although the micelle size was increased, the solubilising environment was less favourable than in bile salt micelles alone. The results serve as a warning to formulators using these surfactants as solubilising agents to consider their likely interactions with endogenous colloidal structures.

Original languageEnglish
Article number119762
Number of pages11
JournalInternational Journal of Pharmaceutics
Publication statusPublished - 15 Oct 2020


  • Bile salt micelles
  • Pluronic
  • SAXS
  • Solubility
  • Surfactant

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