Determination of the bioavailability of clobetasol propionate applied to the skin of human subjects using dermal microdialysis

Abstract

Dermal microdialysis was used to assess the bioavailability of a topical corticosteroid, clobetasol propionate, following application onto the skin of human subjects. The penetration of clobetasol propionate from a 4% m/v ethanolic solution applied onto 4 sites on one forearm of healthy human volunteers was studied. In vitro retrodialysis experiments indicated that there was significant and complete adsorption of CP to the MD probe system components when saline was used as the perfusate, but when a lipid emulsion, Intralipid ® , was used as the perfusate, CP was completely recovered in the dialysate. Linear microdialysis probes with a 2 kDa cut-off were inserted intradermally in human subjects at designated sites. The flux of CP from the extracellular fluid of the skin through the membrane of the MD probe into the perfusate was determined as 0.15 μg/cm 2 .hr and the permeation coefficient was calculated from the equation P = J/C0 and found to be 3.68 x 10 -6 cm/hr where P is the permeation coefficient, J is the flux and C0, the starting concentration which was based on the concentration of CP applied at the site. The results indicated that Intralipid ® could be used as a suitable perfusate for in vivo microdialysis of this lipophilic drug. Furthermore, the study clearly demonstrated the application of dermal microdialysis as a valuable tool to assess the bioavailability/bioequivalence of clobetasol propionate penetration into the skin following topical application.