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% HPbetaCD. The permeability and flux of the drugs though a PAMPA membrane at different unstirred water layer (UWL) thicknesses was determined. In absence of HPbetaCD, permeability coefficients increased two- to three-fold with decreasing UWL thickness to a certain minimum values of about 40 microm. Addition of HPbetaCD to systems exhibiting larger UWL thicknesses significantly increased compound flux. The effect of HPbetaCD was linked to its association constant (K(1:1)) 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.
Brewster
Marcus E
ME
Chemical and Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Noppe
Marc
M
Peeters
Jef
J
Loftsson
Thorsteinn
T
D000465:Algorithms; D002021:Buffers; D002220:Carbamazepine / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000737:chemistry*; D004058:Diffusion; D006118:Griseofulvin / Q000737:chemistry; D006854:Hydrocortisone / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D010539:Permeability; D012996:Solutions; D014867:Water
D002021:Buffers; D003505:Cyclodextrins; D008567:Membranes, Artificial; D012996:Solutions; D014867:Water; D006118:Griseofulvin; D002220:Carbamazepine; D006854:Hydrocortisone