Influence of penetration enhancers on the blanching intensity of betamethasone 17-benzoate

Abstract

The influence of various potential lipophilic penetration enhancers on the blanching intensity of the model drug betamethasone 17-benzoate is examined with respect to the thermodynamic activity of the drug in the vehicle. The parameter of response is the relative intensity of blanching. The penetration enhancing effects of the vehicles are quantified using two different parameters. The first is the activity-standardized bioavailability factor determined from activity-response lines, which 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 thermodynamic drug activity, determined from activity-response lines and from one-point measurements applying suspensions. Both penetration enhancement-describing parameters show a linear correlation with the solubility of the model drug in different vehicles. This requires a substantial penetration of the vehicles themselves to be able to act as cosolvents in the stratum corneum. Penetration enhancement by this mechanism is only possible if the drug shows differentiated affinities to lipophilic, stratum corneum-like vehicles. Betamethasone 17-benzoate formulations with low drug solubility, solutions as well as suspensions with a low amount of solid in the vehicles, show drug depletion effects.