Effect of the unstirred water layer on permeability enhancement by hydrophilic cyclodextrins

Saturated solutions of three test compounds, carbamazepine, griseofulvin and hydrocortisone, were prepared in aqueous buffer (pH 7.4) containing 0, 1, 5 and 10% HPβCD. The permeability and flux of the drugs though a PAMPA membrane at different unstirred water layer (UWL) thicknesses was determined. In absence of HPβCD, permeability coefficients increased two- to three-fold with decreasing UWL thickness to a certain minimum values of about 40μm. Addition of HPβCD to systems exhibiting larger UWL thicknesses significantly increased compound flux. The effect of HPβCD was linked to its association constant (K1:1) with the model drugs and decreased with decreasing UWL thickness to a certain minimum value. This suggests that hydrophilic cyclodextrins enhance flux when the UWL resistance significantly contributes to the overall barrier resistance.