The role of surfactants in the release of very slightly soluble drugs from tablets.

The ability of surfactants to accelerate the in vitro dissolution of very slightly soluble drugs has been ascribed to wetting and/or micellar solubilization. Deflocculation as a mechanism to accelerate dissolution has not been investigated. In the present study, the effect of a surfactant on the dissolution kinetics of prednisolone from tablets and the mode of action of the surfactant were investigated. The dissolution of prednisolone at 37 degrees in 0.1 N HCl containing different concentrations of the nonionic surfactant, octoxynol 9, followed zero-order kinetics. The rate constant was increased by 15, 150, and 950% when octoxynol was added to the dissolution medium at 0.0039 and 0.032% (approximately 0.5 and 4.0 times the critical micelle concentration) and incorporated into the tablets (for a final concentration of 0.0039%), respectively. The surface tensions of the dissolution media were 71, 35, and 31 dyne/cm for 0, 0.0039, and 0.032% octoxynol, respectively. The largest decrease in surface tension corresponded to the smallest increase in dissolution rate, indicating that wetting was unimportant. The micellar solubilization capacity of octoxynol was much too small to account for the increases in dissolution rate. Microscopic particle size measurements and sedimentation volume determinations showed the pronounced deflocculation of prednisolone by the surfactant. The observed increases in specific surface area at the two octoxynol concentrations were in good quantitative agreement with the increases in dissolution rate according to the Noyes-Whitney equation.