Based on an investigation on furbiprofen solubilization in polysorbate 80 solutions at different pH, this study proposed an equilibrium-based model to characterize the drug-surfactant interactions in pH controlled system. The model reflected both interactions and interdependence among all drug-containing species: unionized drug in water D(u), ionized drug in water D(i), unionized drug in micelles D(u)M, and ionized drug in micelles D(i)M. The micelles were defined and quantitated as the micellized surfactants, so both D(u)M and D(i)M were also seen as unionized and ionized drug associated with micellized surfactants. This mathematical treatment enables the modeling of the drug solubilization in pH-surfactant solutions without making unsound approximations. Using a separate set of solubility data at a different pH, a comparison was conducted between experimental data and the solubility estimated by this model, and by the partition model proposed by Rippie et al. It was found that both models yielded reasonably good estimation compared with experimental data. It was also found that the solubility data estimated by the proposed model were more reliable especially when the surfactant concentration was high in the system. This suggests that the consideration of interrelations and interdependence of all drug species in pH-surfactant solutions by this model is justified and appropriate.