EXPERIMENTAL STUDIES ON PERCUTANEOUS ABSORPTION 251 which is dependent upon a variety of physical factors: in vitro one can work with epidermal or stratum corneum membranes and turn them round, it does not really matter which way you have the membranes. The assumption is made in relation to DMSO, aso, that if large amounts of water pour out through an anhidrotic epidermis, then the barrier is impaired and similarly the barrier would be impaired for any molecules trying to go the other way. There is a good deal of experimental evidence by Kligman and others that this is so DMSO will enable almost anything to penetrate the skin in vastly increased amounts, so these are two separate factors and in certain circumstances they will pull against each other. As to the actual mechanism of the way in which DMSO works, this is not too clear one hypothesis is that it does so by greatly increasing the hydralion of the stratum corneum and it is feasible that this is the main factor. We know, for instance, from the original vasoconstriction studies of Mackenzie and Sloughton (4), that hydrating the stratum corncure under polythene can reduce the threshold concentration of asteroid producing vasoconstriction by a factor of 100 so that there is no reason to disbelieve the proposition that this sort of hydralion can have a very dramatic effect. There is one hypothesis which is really the direct opposite, and this is that DMSO, because of its affinity for water, is in fact dehydrating the stratum comeurn and altering the physical-chemical state of the barrier and, therefore, doing something which allows molecules through. This problem, as far as I know at the moment, has not been resolved. MR. N.J. VA• ABB•: Your data in Table I on the partial occlusivity of a base containing solids. such as zinc oxide, has been referred to once or twice in the literature as being a means of not occluding too much with an ointment, but I do not think I have seen data before and I wonder if you have, or would like to say what effect, for instance, the particle size of the zinc oxide has, or the method of processing the paste, which could obviously make a big difference to the aggregate size of the zinc oxide. Could one get a whole range of different occlusivities according to the way in which a paste is made? T•E L•cTrmEm There certainly would be some variation. 1 have not done this, it is time-consuming and this is just a question of repeating the experiment under a variety of different conditions and I do not know of any other work that has been done on this point, I would expect only minor variations, and I doubt whether one would get differences of much more than + 25%. I use one compound zinc paste that is made up by our pharmacist for clinical use. M•. J. D. Mm•ETON: One knows that DMSO is a highly hygroscopic coinpound and would be expected to pick up water not only from the deeper layers of the skin but also from the atmosphere. Are DMF and DMA hygroscopic? Can you explain their action on this basis? I know that they are miscible with water but I am not sure about their hygroscopic properties. TaE LECTURER: All three are hygroscopic. Also when DMSO, for instance, is mixed with water one gets heat of hydralion and this has a small effect on the stratum corneum temperature. We know, according to simple physical laws, that the temper- ature of the membrane is one of the factors which determines the penetration of molecules through it. The only point is that at the moment no-one has demonstrate{l, or been able to measure, the exact degree of hydralion produced by DMSO.

252 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS DR. J. J. MAUSNER: I was very interested to see your results with lanolin. This has been used in this industry as an occlusive par excellence for many years and it is somewhat surprising to see that you have recorded total non-suppression with anhydrous lanolin. Could it be possible that these results might be changed or possibly reversed in the presence of other ingredients such as •vater for example, or in an emulsified system? THE LECTUREm They certainly would be altered but i can not conceive that they would be reversed we know that soft white paraffin is almost completely hydro- phobic. Lanolin can be mixed with water and water-containing systems, and I would think that it is physically possible to explain the movement of water across a lanolin barrier. I agree that both emulsifying ointment B.P. and lanolin have been regarded as being occlusive in the past I think it is a little surprising how completely non- occlusive they were under the conditions of this experiment. De. D. SPRUYT: I suggest that you measure the water vapour loss through lanolin, calculate the resistance and you will get your answer.