- Although the extraordinary solubility advantage afforded by cyclodextrins has led to their widespread use as pharmaceutical solubilizers, several reports have emerged that cyclodextrins may also reduce the apparent permeability of the drug. With the purpose to investigate this solubility–permeability interplay, we have recently developed a mathematical mass transport model that quantitatively explains the impact of molecular complexation on the intestinal permeability. This model enabled excellent quantitative prediction of progesterone P eff as a function of HPβCD concentrations in several experimental methods. The purpose of the present study was to challenge the predictive capabilities of this mathematical model, assessing whether the model allows the prediction of literature permeability data, as a model validation method. The mass-transport model was applied to carbamazepine and hydrocortisone, and the predicted permeability ( P eff , P m and P aq ) vs. HPβCD concentration were plotted. Excellent agreement was obtained between literature experimental permeability and the predicted P eff values for both compounds at all of the HPβCD concentrations tested. The presented validated model that considers the opposing effects of the formulation on the solubility and the permeability, can lead to a more efficient and intelligent use of molecular complexation strategies; the formulator will be able to a priori strike the optimal solubility–permeability balance to maximize and facilitate the overall oral drug absorption.