Abstract: AimTo investigate the combined effect of cosolvent and cyclodextrin (CD) on solubilization of insoluble drugs. MethodsPhase-solubility method was applied to determine solubilization of two diterpenoids in cosolvent / cyclodextrin combinations. The combined effect was evaluated and explained with an established mathematical model, and the model parameters were calculated by means of nonlinear regression analysis. ResultsThe strong agreement between the predicted and the observed solubility data supports the validity of the proposed model, with the determination coefficients of two regression models were 0.993 and 0.992, separately. ConclusionThe validated mathematical model can be used to explain and predict the combined solubilization of the two insoluble drugs in different cosolvent systems.