INFLUENCE OF PENETRATION ENHANCERS ON THE BLANCHING INTENSITY OF BETAMETHASONE 17-BENZOATE

The influence of various potential lipophilic penetration enhancers on the blanching intensity of the model drug betamethasone 17-benzoate i s examined with respect to the thermodynamic activity of the drug in t he vehicle. The parameter of response is the relative intensity of bla nching. The penetration enhancing effects of the vehicles are quantifi ed using two different parameters. The first is the activity-standardi zed bioavailability factor determined from activity-response lines, wh ich equals the enhancement ratio. The highest value found was 6.4. The second parameter is the activity-standardized vertical distance, that is the difference of the response of preparations with equal thermody namic drug activity, determined from activity-response lines and from one-point measurements applying suspensions. Both penetration enhancem ent-describing parameters show a linear correlation with the solubilit y of the model drug in different vehicles. This requires a substantial penetration of the vehicles themselves to be able to act as cosolvent s in the stratum corneum. Penetration enhancement by this mechanism is only possible if the drug shows differentiated affinities to lipophil ic, stratum corneum-like vehicles. Betamethasone 17-benzoate formulati ons with low drug solubility, solutions as well as suspensions with a low amount of solid in the vehicles, show drug depletion effects. (C) 1998 Elsevier Science B.V. All rights reserved.