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CONSIDERABLE knowledge has been gained from the investigation of the percutaneous absorption of steroids and other pharmacologically active substances. The infiuence of pharmaceutical formulation on percutaneous absorption is less understood and, although it is widely believed that the vehicle can influence penetration and the amount of the substance absorbed, there is little precise information regarding the effect of formulation. Williams (1964) has pointed out that there is no " solid scientific evidence to guide the prescription of an active ingredient in a lotion, an ointment, a paste or a cream ".Using methyl nicotinate as a marker substance, the influence of the four main types of vehicles has previously been studied (Barrett et al., 1964a). The results show that methyl nicotinate is released equally quickly from an oil-in-water and a water-in-oil cream, but that it is released more slowly from white soft paraffin and markedly more slowly from macrogol ointment. This work has been extended and in this paper we give experimental and clinical findings on the absorption of eorticosteroids from various vehicles. INVESTIGATION.The occlusion technique of McKenzie and Stoughton (1962) has been adapted to measure the penetration from different vehicles of betamethasone-17-valerate, fluocinolone acetonide. hydrocortisone acetate and hydrocortisone alcohol.The vehicles used were : (i) Aqueous Cream B.P., containing 30% Emulsifying Ointment B.P., O'l% chlorocresol and 69-9% purified water, i.e. an oil-in-water cream.(ii) Oily Cream B.P., containing 50% Ointment of Wool Alcohols B.P. and 50% purified water, i.e. a water-in-oil cream, (iii) White Soft Paraffin B.P.(iv) Carbowax 1500-a blend of equal quantities of polyethylene glycol 300 and 1540, i.e. a water soluble ointment.The eorticosteroids were prepared in the various vehicles in a range of concentrations. Equal volumes of these materials were applied to a standard area of skin using the technique and applicator previously described in this journal (Barrett et al., 19646). The sites were occluded with polythene film for sixteen hours and the degree • of the resulting paUor scored subjectively on a scale of 0-3. RESULTS.(i) Betamethasone-H-valerate.-Two concentrations, 0-1 and 0-05%, of betamethasone-17-valerate in each of the four standard vehicles described above were studied. The mean results in ten subjects are given in Table I. They

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We have studied the transdermal absorption of tritiated fentanyl (citrate and base) and sufentanil citrate. Approximately 50 micrograms of drug in water was applied to the forearm skin of volunteers (5 subjects for fentanyl citrate and base, 6 for sufentanil). When the water had evaporated the site was covered with an occlusive dressing. Total urine collections were carried out for 96 h in 12 h periods. At 24 h the dressing was removed and skin removed with serial applications of adhesive tape. The radioactivity in the urine and on the tape was measured in a scintillation counter. Urine recovery expressed as a percentage of the absorbed dose was 17.9 +/- 1.9% for fentanyl citrate, 20.5 +/- 5.6% for fentanyl base, and 22.5 +/- 2.5% for sufentanil. In one subject who ran 10 miles with a sufentanil patch in situ the recovery was 52.3%. The systemic availability of fentanyl by this route is approximately 30% of that found using the intravenous route.