248 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS from the water vapour loss in mg cm-2 h-1. In Table II the resistance has been cal- culated from the estimated water vapour loss of some experiments. Table II Measurement of the permeability of skin at 33øC at 23øC (E----64 kJ mole-') 0.01 mm thick layer of SWP soft white paraffin at 33øC at 23øC forearm skin id q- SWP for 15 min t h later It h later 2• h later 4 h later (+ sweating) Water vapour loss found in mg cm -2 h -1 0.20 0.09 0.21 0.09 0.60 0.054 0.192 0.150 0.144 0.27 Occlusivity complete partial complete complete partial Resistance to water vapour loss in 103 s cm-• 0.63 0.81 0.60 0.83 0.21 2.3 0.66 0.84 0.88 0.47 Increased barrier quality 1 x (nothing) 11x 3.1x 4.0x 4.2x 2.2x The SWP permeability has been calculated from measurement at a 2.7 mm layer of SWP. The values indicate that the barrier is much increased (11 times) immediately following the application of the SWP. It is increased twice or three times about an hour later when a stationary state has been obtained. This increase can have been obtained by a 0.02 or 0.03 mm thick layer of SWP. As the thickness of the layer of SWP probably has been the same, the explanation of the occlusive effect of the SWP may be its high specific resistance against water evaporation. It has been supposed that the skin is completely flat and that the layer of SWP spread over the skin has the same thickness everywhere. However, at the sweat duct opening the absorbed layer of SWP may be thicker than at normal stratum corneum. I wonder whether a failure of the correlation of the experimentally found water vapour loss of SWP-treated skin with the summation of the water vapour loss of the non-treated skin and the layer of SWP might provide some information about such phenomena. According to your definition, "occlusivity" will be obtained by the spreading of a layer with a water vapour loss to less than 25% of the skin's TEWL ("complete suppression"). Accordingly the resistance of this layer will have to amount to three times the resistance of the investigated skin and it therefore depends on the TEWL of the investigated skin. I should like to know whether this "occlusivity" has to be chosen as a criterion or the average thickness of the relevant layer of occlusive material (SWP). Maybe "occlusivity" is medically preferred and "increase of re-

EXPERIMENTAL STUDIES ON PERCUTANEOUS ABSORPTION 249 sisrance" is physically preferred. Quantitatively the "occlusivity" is perhaps repre- sented by the increase of the barrier quality as proposed in Table II. THE LECTURER: We did make some calculations on the thickness of these layers and in the case of soft white paraffin I estimated the layer thickness as about 0.05 ram. The reason why the results are not expressed in relation to a standard thickness of a vehicle is because although this may be desirable from the point of view of the physicist, in practice the thickness of a layer applied therapeutically is going to depend upon the nature of that material, its density and viscosity, and one wants to get a comparison of occlusive potentials as they would actually be in clinical circum- stances. With regard to occlusivity versus resistance, there is no doubt that your measurement of resistance is more precise from the physical-chemical point of view the reason that occlusivity was used is that this parameter--as I have defined it---is related to the amount of water diffusing across the stratum corneum. If transepider- mal water diffusion were negligible, it would not matter how high the resistance of a vehicle layer applied would be, this would not result in any significant hydration of the stratum corneum and, therefore, would not result in any increased percutaneous absorption of the penerrant. From the biological point of view, the thing that matters is the combination of the resistance with the transepidermal water loss and the result of these two factors on the hydration of the stratum corneum itself. MR. J. •,V. HADGRAFI: I was very interested in your results with tetrahydro~ furfuryl alcohol, dimethylacetamide and propylene glycol, and I wondered whether you had in fact done similar experiments with different concentrations of these solvents, since if it is an effect of the solvent on the area function of the skin, one might expect that it would be related to concentration. THE LEClURER: I think it is related to concentration you will remember that these experiments were done on the normal forearm skin of humans these in fact were patients who had conditions of various sorts elsewhere and who were acting as volun- teers. If one uses higher concentrations you may or do get into the realm of primary irritation reactions on the viable epidermis and the dermis therefore you are liable to produce a reaction which is intolerable to the patient, or one which is not fair to inflict on the volunteer. We have carried out some experiments with lower concen- trations, with 15% THFA, for instance, and lower concentrations of DMA, and found slight diminishing. 15% THFA, for instance, did not have any significant effect on the transepidermal barrier. With DMSO and DMA there is the problem of the hydration of the DMSO molecule itself and one has to maintain the concentration of DMA in relation to the amount of water in the system, otherwise one effectively has no material present. MR. N.J. VAN ABBg: Would you like to comment on the clinical significance of doing the measurements of occlusivity under conditions of suppressing sweating? Surely these bases would not normally be used in practice under such conditions, and it would be interesting to have your view on the clinical significance of this. THE LECTURER: For experimental purposes one has to try and separate the factors, and using this particular parameter one cannot, of course, work if there is sweating. If under normal circumstances the skin is sweating, in clinical circumstances this will