j. Soc. Cosmet. Chem., 37, 397-407 (November/December 1986) The skin plasticisation effect of 2-hydroxyoctanoic acid. I' The use of potentiators K. J. HALL and J. c. HILL, Unilever Research, Port Sunlight Laboratory, Quarry Road East, Bebington, Merseyside L63 3JW, United Kingdom. Received June 2, 1986. Synopsis The plasticisation of stratum corneum by 2-hydroxyoctanoic acid (HCA) has been studied as a function of ambient relative humidity, solution pH, sorption, penetration, and the presence of added penetration enhancers and structurally related materials. Experiments were performed in vitro using guinea pig footpad epidermis for flexibility measurements and human stratum corneum for sorption and diffusion measure- ments. Plasticisation was maintained over the entire range of relative humidities studied (30-80%). Enhanced skin flexibility may thus be achieved even at low relative humidity where skin dryness is more prevalent. As pH of the HCA solution is increased, the plasticisation effect, sorption, and penetration all decrease. Extensibility was found to be a linear function of free acid penetration. The addition of penetration enhancers and structurally related materials can give substantial increases in HCA efficacy (up to 9-fold). These additives do not substantially affect extensibility on their own. They thus act by potentiation, not synergism. There was no simple relationship between potentiation and increases in penetration or sorption of HCA. INTRODUCTION The importance of skin flexibility in maintaining a soft and supple skin with the min- imum of superficial dryness/flakiness has been widely recognised in the literature (1). Blank's pioneering work in this field showed that the flexibility of the skin can be increased by increasing its water content (2). For this reason, the classical approach for treating and preventing dry skin is to increase its water content with moisturisers. Such materials can act by two different mechanisms: © occlusion, i.e., the application of a water-retardant barrier which increases skin water content by reducing transepidermal water loss (3). © humectancy, i.e., increasing the skin's water-binding capacity by the application of hygroscopic materials (4). However, more recent studies have shown that skin flexibility can be increased by a number of materials other than water. These are generally termed plasticisers and in- 397

398 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS clude alcohols (5), hydrogen-bond breakers such as urea and lithium bromide (5), and hydroxy acids (6,7). Takahashi eta/. (5) studied C•-C 5 alcohols and found that the skin plasticisation effect falls off rapidly with increasing chain length. However, the short chain alcohols are of little product interest due to their volatility, which might severely limit the duration of skin plasticisation i, vivo. An investigation of hydroxyacids by Takahashi eta/. (6) showed that they are better skin plasticisers than both alcohols and fatty acids. (x-Hy- droxyacids were more effective than [3 ones. Plasticisation increased with increasing chain length up to C4, but no further improvement was noted in the range C 6 to C 8. However, the C 6 and C 8 hydroxyacids tested were branched and aromatic, respectively therefore, no conclusions concerning chain length dependence above C4 may be drawn from these observations. Alderson eta/. (7) examined C 3 to C•o (x-hydroxyacids, all of which had n-alkyl chains. They found the maximum increase in skin extensibility for 2-hydroxyoctanoic acid. From the results of water-binding studies they suggest that hydroxyacids may occupy sites in the stratum corneum which are normally occupied by water molecules. Studies carried out by the current authors have confirmed this chain length dependence, but it is important to remember that as the chain length of these acids increases above 8, their solubility rapidly decreases and this will become a limiting factor in the delivery of their plasticisation efficacy. Both Takahashi eta/. and Alderson eta/. attribute the plasticisation effect to a reduction in the interaction between polar groups of keratin chains in skin, due to reductions in hydrogen bonding (5-7). This study considers in more detail the dependence of skin plasticisation by 2-hydroxy- octanoic acid on relative humidity, pH, sorption, penetration, and the presence of added penetration enhancers and structurally related materials. EXPERIMENTAL PROCEDURE PREPARATION OF STRATUM CORNEUM FOR EXTENSIBILITY MEASUREMENTS Stratum corneum is readily obtainable from the rear footpads of guinea pigs. The prepa- ration procedure differed from that commonly used (8) as we considered that the tech- nique of enzyme separation (involving lengthy exposure to an aqueous solution con- taining the enzyme trypsin and urea) would result in an unacceptably large modification to the mechanical properties of the skin (9, 10). For the same reason further extraction of lipids with organic solvent was not carried out. The dissected footpads were wrapped in small pieces of thin aluminium foil and immersed in water at 60øC for 3 minutes. It was then an easy task to separate with forceps an intact epidermis layer. The samples were to be subsequently immersed in water and aqueous test solutions for 3-hour pe- riods. Following such immersion we found that it was possible to easily scrape away the softened epidermal cells to leave a layer consisting almost entirely of stratum corneum (callus). When measurements were made to compare the mechanical properties of whole epi- dermis with those of stratum corneum, little difference was found. We therefore carried