Solubilization and wetting effects of bile salts on the dissolution of steroids

Abstract

The ability of sodium taurocholate to increase the initial dissolution rate of five steroids was studied in terms of effects on solubility, wetting, and diffusion coefficient. For all compounds, wetting effects predominated over solubilization effects at bile salt concentrations representative of the fasted state. For hydrocortisone, triamcinolone, betamethasone, and dexamethasone, this trend also continued at the higher bile salt concentrations typical of the fed state. Bile salts solubilized these compounds by a factor of two or less, and diffusivity changes were negligible at bile salt concentrations up to 30 mM. For the more lipophilic danazol, the wetting effects were small and of importance only at premicellar levels of bile salt. At higher concentrations, the increase in solubility was the predominant factor. Incorporation into micelles appeared to decrease the diffusivity slightly, but this was important only at bile salts concentrations of 15 mM or higher. In conclusion, it appears that even within a series of structurally related compounds the mechanism by which bile salts mediate increases in dissolution rate can differ considerably.