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

• Published in: Drug development and industrial pharmacy Vol. 44; no. 4; pp. 677 - 686
• Main Authors: Vinarov, Zahari, Katev, V., Radeva, D., Tcholakova, S., Denkov, N. D.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.04.2018
• Subjects: hydrophilic head; hydrophobic chain; Hydrophobic drugs; solubilization locus; surfactant micelles; Hydrophobic drugs; hydrophilic head; surfactant micelles; hydrophobic chain; solubilization locus
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2017.1408642

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.