Micellar solubilization of poorly water-soluble drugs: effect of surfactant and solubilizate molecular structure

Abstract

Objective: This study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant solutions.

Significance: (1) Rationale for surfactant selection is provided; (2) the large data set can be used for validation of the drug solubility parameters used in oral absorption models.

Methods: Equilibrium solubility of two hydrophobic drugs and one model hydrophobic steroid in micellar solutions of 19 surfactants was measured by HPLC. The drug solubilization locus in the micelles was assessed by UV spectrometry.

Results: Danazol is solubilized much more efficiently than fenofibrate by ionic surfactants due to ion–dipole interactions between the charged surfactant head groups and the polar steroid backbone. Drug solubilization increases linearly with the increase of hydrophobic chain length for all studied surfactant types. Addition of 1–3 ethylene oxide (EO) units in the head group of dodecyl sulfate surfactants reduces significantly the solubilization of both studied drugs and decreases linearly the solubilization locus polarity of fenofibrate. The locus of fenofibrate solubilization is in the hydrophobic core of nonionic surfactant micelles and in the palisade layer of ionic surfactant micelles.

Conclusions: Highest drug solubility can be obtained by using surfactants molecules with long chain length coupled with hydrophilic head group that provides additional drug–surfactant interactions (i.e. ion–dipole) in the micelles.

Keywords:

• Hydrophobic drugs
• surfactant micelles
• solubilization locus
• hydrophobic chain
• hydrophilic head

Acknowledgments

The insightful discussions with Dr. Svetoslav Anachkov, Prof. Todor Dudev and Prof. Stoyan Smoukov are gratefully acknowledged. The authors also thank Ms. Monika Kovadjieva for measuring the UV-spectra of fenofibrate in solvents and surfactant solutions.

Disclosure statement

The authors report no conflicts of interest in this work.

Additional information

Funding

The partial financial support of Project No. 80–10-225/25.04.2017 of Sofia University Research fund, and European Research Council (ERC) grant to Stoyan K. Smoukov, EMATTER (# 280078) is also gratefully acknowledged.