9.00 JOUBNAL OF THE SOCIETY OF COSMETIC CHEMISTS twice the normal loss. In erythroderma the water loss was 14 times the normal (53). This is quite apart from sweating and is essentially outside the control of body mechanisms. Apart from its effect on water and salt metabolism, the evaporation of this amount of water from the skin surface requires over 1000 calories, a formidable daily energy requirement of patients who are ill (60). The state of hydration of the stratum corneum has been accepted for quite some time as of major importance in influencing percutaneous absorption. Wurster and Kramer (16) measured the rate of penetration of esters of sali- cylic acid through skin with dry and hydrated stratum corneum. They found that when the tissue was hydrated the rate of penetration of the most water- soluble ester increased more than that of the other esters studied. Working with aspirin in a temperature-humidity chamber, Fritsch and Stoughton (27) showed the dual importance of these factors on the penetration of excised skin. Full hydration of the keratin, accomplished by layering water over acetylsalicyclic acid on the epidermal surface, dramatically increased the penetration when compared to conditions of lower humidity at the same temperature. The importance of hydration can also be found in those investi- gations employing occlusive plastic film in steroid therapy. Here, the preven- tion of water loss from the stratum corneum and the subsequent increased water concentration in this skin layer enhances the penetration of the steroid (23, 29-32). McKenzie and Stoughton (29) have shown that penetration of corticosteroids may be increased 100-fold by occluding the site of application and thus hydrating the stratum corneum. It is also quite probable that some drugs increase the degree of hydration of the skin. This is most likely to occur with substances that readily penetrate the skin, and thus reach sufficiently high concentrations to produce an osmotic effect. A few steroids, such as es- trogens and pregnenolone, have been reported to produce a beneficial effect on aging skin by hydrating the skin (66, 67). Topically applied vehicles have the potential to either increase or decrease the quantity of water in the horny laver. The efficiency of varied type vehicles in aiding penetration can be reasonably predicted on the basis of their effect on hydration of the stratum corneum or how the vehicle alters the activity of water in the stratum corneum and influences the stratum corneum/vehiele partition coefficient. Water-insoluble, oily materials such as petrolatum, lano- lin, and isopropyl myristate significantly retard the rate of loss of water from the skin surface. On the other hand, certain emulsifiers and humectants in- crease the rate of moisturc loss (7, 68-70). Skin keratin has an isoelectric point of 3.7-4.5. Hence, it would appear that hydration would be affected by changes in pt. Yet, there are litfie data to support the idea that the pH of vehicles within the range tolerated without immediate irritation or skin damage affects the hydration state of skin greatly (16). Studies of stratum cornea from varied species (13, 15, 71) showed very little change in the swelling or hydration characterishcs of skin between pH

XVATER AND THE SKIN 201 values of 1--10. Significant increases in water diffusion rates and decreases in water-binding capacity were observed with buffer solutions at)ove pH 10, and primarily at pH 12. These changes at high pH values can be attributed to ex- traction of water-binding substances and the solubility of keratin in the pH range 10-12. Diffusion of water through the stratum comeurn is a purely passive process affected only by physical factors as determined by ambient conditions, chiefly the water vapor pressure gradient across it (7, 8, 10, 72-77). The permeabil- ity constant of water in the skin at 25øC is approximately 0.5 x 10-acm/hr, corresponding to a flux of 0.2 mg/cm2/hr (5). The flux is approximately the same whether liquid water or saturated water vapor is applied in vitro. These data suggest that the surface concentration, which is not very different in these two instances, controls the diffusion rate and this is good evidence that water transport through skin is a passive process (10). There is little or no evidence to support specialized active transport for cells of the stratum comeurn. In order for water to move against a concentration gradient, an energy yielding "pump" is predicated in a viable epidermis. It certainly is un- likely that such a reaction would exist in a nonviable tissue like the stratum comeurn, and there is limited evidence for any transport across the stratum corneum against a concentration gradient. It appears that the major route of absorption of water during steady-state diffusion is transcellular through '%oundwater" regions in the hydrated stratum corneum (78, 79). The practi- cal and theoretical considerations involved in studying water transport through the stratum comeurn are analagous to those of studying transport through monomolecular layers (57). However, the mechanism of transport through hydrated stratum corneum may be quite different from that through normal stratum comeurn. The low diffusion constant and high activation energy obtained for water suggest that extensive hydration does not dras- tically affect the "barrier" function of the stratum comeurn (20). The more important point to consider is the thermodynamic activity of water in the barrier phase, not just the amount there. WATER BINDING The normal appearance of skin and its ability to resist environmental irri- tants, both physical and chemical, are attributable to a large degree to the capacity of the corneum layer to bind water (13). The stratum corneum has a natural ability to hold a certain amount of water against the diffusion gra- dient created by adverse ahnospheric conditions such as low dew points (7, 44). Most of our information on water-binding results from interpretation of solvent extraction of the skin. Little change occurs in either the water-bind- ing capacity in a humid atmosphere or in the weight of human callus when it is extracted with water or with polar lipid solvents such as pyridine. How-