238 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS its rate of penetration is very high. This is partly because the ester does not set up an electrostatic barrier. It must, however, be mentioned that it is also more oleophilic than the acid. A most illuminating finding is, however, the instance of nicotinic acid. This substance, when applied as a dilute solution in water, will produce pinking of the skin due to its vaso-dilatory action on the surface capillaries. The effect varies from person to person. It was found that its action could be measured by using two thermo-couples separated at a small distance and measuring the differential temperature between the treated and the non- treated areas of the skin. When an ester of nicotinic acid, e.g., tetrahydro- furfuryl nicotinate, was applied, the reaction was considerably enhanced and also prolonged. This ester is soluble in oil as well as in water. It was subsequently dissolved in white mineral oil and on application to the skin the vaso-dilation was pronounced and prolonged. Some time later the experiment was repeated, but no reaction was observed. My colleague, Mr. Powell, fortunately recollected that at the time of the earlier work the conditions in the laboratory were distinctly hot and humid. He decided that the moisture on the skin might be a factor. After skipping for 15 minutes in order to induce sweating, he found that the application of an oil solution of the tetrahydrofurfuryl nicotinate produced a pink patch and an increase in the temperature of the surface of the skin. This was an important find- ing, and its implications will be discussed later. There has been much published work on the choice of the "oil" v•hich is most efficacious for "feeding" the skin. This was briefly discussed by the author.' It was pointed out that liquid paraffin was by no means the best substance with which to anoint the skin, for the simple reason that it does not spread over the surface of a water-wet material. If the surface is dry or is already wetted by fat then it will do so and, indeed, if massage be applied it will dissolve or blend with the fatty material, soften it and enable it to be removed by means of a tissue. For the purposes of cleansing it can function quite well, especially as it is not such a good solvent that the skin will be denuded of sebaceous fat. Nevertheless, the addition to the mineral oil of a polar fat-or even essential oils--will improve matters, and if the added materials are well chosen and in sufficient amount, they can imbue mineral oil with many desirable qualities, and approach those of fixed oils and certain esters. As in leather manufacture, the lower the viscosity at equal spreading power the better is the penetration. The penetration by oily material is probably a two-routed mechanism. It has long been known that greasy ointments require massage even though they be fluid at the temperature of the surface of the skin. This is because the dominant point of entry is via the hair follicles, and the act of massaging forces the oils down the hair follicle, the internal surface of which is fat-

PENETRATION OF SKIN--DEAD AND ALIVE 239 wetted. The wall of the sebaceous gland is dominantly oil permeable and the applied "oil" will reach the cutis vera and the lymphatic system, where it can then eventually enter the blood stream. The other route depends on the ability of the oil to spread over a water- wet surface. If the protein be dry, then the oil, while able to wet the surface, will tend to pile up as a layer of sensible thickness and it will not be able to flow through interstices of infinitely small dimensions, especially if the surface is covered with a film of adsorbed air and the oil is viscous. Under these conditions the oil would find great difficulty in passing through the top layers of the epidermis. On the other hand, massage would be of considerable help, but actual contact with the protein, because of the air surface, would not be at all good unless the oily material was of low viscosity and low surface tension. Although air-dry keratin contains 11 or more per cent of moisture, this water is "bound" and, indeed, is defined as that water which almost seems to be part and parcel of the protein molecule. It is, by definition, not free to dissolve any water-soluble material. In the case of gelatin, it has been shown by various methods that the ':bound" water is of the order of 30 per cent calculated on the total weight, or 1.00 gm. of anhydrous gelatin can bind 0.50 gm. of water. 7 When one realises that hair can only imbibe a total of about 33 per cent of water when in equilibrium with water-saturated air (100 per cent R.H.) it is quite certain that no unbound water is available under conditions where the skin surface is free of sweat. It is clear that the use of water-free oils or vehicles is not a satisfactory method of inunction if penetration is to be accomplished. This is all the more appreciated if the literature is surveyed. Time and again, the water- containing bases produce best penetration of the intact skin, and it was certainly instanced in the experiment already described when using white oil containing an ester of nicotinic acid. (In this instance it was deemed undesirable to use a water-containing base since the ester in the course of time hydrolyses and the preparation loses much of its potency). If then it is necessary to employ a water-free base, the epidermal surface must be anointed with water if penetration of the epidermis is to be achieved. It should be noted that the previous statements refer to water-containing bases in which the "oil" is the continuous phase such as are characterised by hydrous lanolin-containing fats. If these are rubbed on the skin and presuming that the emulsion has been correctly made, they should not throw out water as visible globules. What happens is that as the emulsion is spread as a thin film the water is emitted as vapour through the oil. For example, if a beeswax-mineral oil emulsion be made under conditions which produce a water-in-oil system and this is examined under the microscope as a thin film open to the air, the water globules will be seen to collapse slowly and