Effect of surfactant molecular structure on Progesterone solubilization

Progesterone is a hydrophobic drug (LogP = 3.9) with solubility-limited oral bioavailability. One approach to improve its aqueous solubility is by solubilization in micellar surfactant solutions. We investigate systematically the effect of surfactant molecular structure on Progesterone solubility by using a set of 17 surfactants with different hydrophilic head group charge and variable hydrophobic chain length. Charged surfactants showed highest solubilization capacity, increasing Progesterone solubility from 0.01 mg/mL to above 3 mg/mL, whereas all nonionic surfactants had much smaller effect (0.5 -1 mg/mL Progesterone solubility). The high solubilization of Progesterone in charged surfactant micelles was explained by ion-dipole interactions in the micelle palisade layer. The increase of hydrophobic chain length improved drug solubilization for all studied surfactants, regardless of the type and charge of the hydrophilic head. In respect to the effect of hydrophilic head group, the solubilization capacity of C-12 surfactants decreased in the order SO4- > E1SO4- > N+(CH3)(3) > E3SO4- > SorbEO(20) = E-10 = E-23. Therefore, the best candidates to improve oral Progesterone absorption through solubility enhancement are surfactants with long hydrophobic chain and charged hydrophilic head group (e.g. alkylsulfates). (c) 2017 Elsevier B.V. All rights reserved.