Effects of vehicle and region of application on absorption of hydrocortisone through canine skin

Objective-To determine the effects of various vehicles on the penetration and retention of hydrocortisone applied to canine skin. Sample Population-20 canine skin samples obtained from the thorax, neck, and groin regions of 5 Greyhounds. Procedure-Skin was harvested from dogs after euthanasia and stored at -20 degrees C until required. The skin was then defrosted and placed into diffusion cells, which were maintained at approximately 32 degrees C by a water bath. Saturated solutions of hydrocortisone that contained trace amounts of radiolabelled [C-14]-hydrocortisone in each vehicle (ie, PBS solution [PBSS] alone, 50% ethanol [EtOH] in PBSS [wt/wt], and 50% propylene glycol in PBSS [wt/wt]) were applied to the outer (stratum corneum) surface of each skin sample, and aliquots of receptor fluid were collected for 24 hours and analyzed for hydrocortisone. Results-The maximum flux of hydrocortisone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH, compared with PBSS alone or 50% propylene glycol, with differences more prominent in skin from the neck region. In contrast, higher residues of hydrocortisone were found remaining within the skin when PBSS alone was used as a vehicle, particularly in skin from the thorax and neck. Conclusions and Clinical Relevance-Penetration of topically applied hydrocortisone is enhanced when EtOH is used in vehicle formulation. Significant regional differences (ie, among the thorax, neck, and groin areas) are also found in the transdermal penetration and skin retention of hydrocortisone. Variability in clinical response to hydrocortisone can be expected in relation to formulation design and site of application.