Unexpected phenomena were observed during binary co-permeation experiments (Fig. ). All investigated pharmaceutical substances (regardless of their molar weight, aqueous solubility, lipophilicity or BCS class) had a manifestable and sometimes very strong effect on CF permeation, although these substances are not a priori meant to act as permeation enhancers or retardants, and no such behaviour has been reported for them before. An increase in the asymptotic quantity released of CF was found for binary co-permeation with ASCaq, NXaq, and CClip, whereas a decease was found for HCTZaq, KMaq, HCTZlip, and APIXlip (Fig. ).