EXPERIMENTAL STUDIES ON PERCUTANEOUS ABSORPTION 241 pre-treatment value) "partial suppression" (reduction of normal or abnormal TEWL to less than 50% of the pre-treatment value) and no significant suppression (less than 50% reduction). The results are summarised in Table I. They show that in the order of thickness likely to be achieved therapeutically, a layer of hydrophobic soft white paraffin is highly occlusive. Compound zinc paste and ung. emulsi- ricans are weakly occlusive. Preparations containing lanolin had no signifi- cant occlusive effect. If TEWL is obstructed, stratum corneum hydration is increased. This temporarily leads to increased water loss when the layer is removed, e.g. by wiping with alcohol, the rate of loss rapidly returning to the pre-treat- ment level. The latter could be achieved in all cases if the vehicle layer was removed within 2 h of application. The occlusion effect demonstrated was not a 'latent period effect'. If the layer was not removed, suppression of TEWL was demonstrable up to 16 h after application. DIRECT PHYSICO-CHEMICAL EFFECTS ON STRATUM CORNEUM The possible influence of a number of agents which have been proposed as pharmaceutical vehicles, mainly as solvents, has been assessed by noting the effect of their application on TEWL. In the absence of sweating and fluctuating corneous hydration the latter constitutes one parameter by which stratum corneum barrier function can be assessed. The following substances were studied. 1. Dimethylsulphoxide (DMSO). 2. Dimethylformamide (DMF). 3. Dimethylacetamide (DMA). 4. Tetrahydrofurfuryl alcohol (THFA). 5. Propylene glycol. The ability of DMSO to facilitate percutaneous absorption of a variety of substances is well established but the duration and degree of reversi- bility of the action have not been established. The following experiments were designed to assess the degree and duration of barrier suppression induced by DMSO and two other similar solvents, DMF and DMA. DMA has previously been incorporated as a solvent in experimental bases for topical steroids (3). TEWL was measured on anhidrotic skin as before. For the experiments with pure DMSO, DMF and DMA 2 ml of solvent were then applied to

242 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 16 cm2 of skin on the flexor forearm and left in situ for 30 min. At the end of this period the skin was wiped dry, exposed to room air for 30 min and to a stream of dry nitrogen for a further 30 min to ensure that no occlusive effect induced by the application interfered with subsequent measurements. TEWL from the anhidrotic test area was then measured la x, 3, 4ax, 6ax and 24 h after first application of the solvent. The results for 100% DMSO, DMF and DMA respectively are shown in Figs. 1-3, and the average effects compared in Fig. 4. 1.8 1.5 1.0 EFFECT OF DIMETHYLSULPHOXIDE ON TRANS-EPIDERMAL WATER LOSS FLEXOR ASPECT OF MID-FOREARM NORMAL ANHIDROTIC SKIN THREE SUBJECTS 2 4 6 8 12 16 20 TIME AFTER EXPOSURE ( HOURS ) Figure 1 Effect of dimethylsulphoxide on transepidermal water loss. The above results refer to the effect of the pure solvents. Further experiments were performed using a cream containing 25ø//0 DMA, 10% water and 650//0 of cetomacrogol emulsifying ointment B.P.C. (DMA cream) 25% tetrahydrofurfuryl alcohol (THFA) in water 50//0 propylene glycol in water. The aim of these latter experiments was to ascertain whether any of the enhancing influence of DMA and THFA in these concentrations on per-