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i j. $oc. Cosmet. Chem., 34, 327-334 (September/October 1983) Evaluation of solvent-skin interaction in percutaneous absorption JOEL L. ZATZ, Department of Pharmacy, Rutgers College of Pharmacy, P.O. Box 789, Piscataway, NJ 08854 and UMESH G. DALVI, E. R. Squibb and Sons, Inc., P.O. Box 191, New Brunswick, ?qj 08903. Received May 6, 1983. Presented at the 12th Congress of the International Federation of Societies of Cosmetic Chemists, Paris, September 1982. Synopsis A method for quantitating solvent-skin interaction in percutaneous absorption under steady state conditions has been developed. In the absence of interactions with the membrane, the maximal flux from saturated solution,Js, is independent of the solvent. Differences in value of Js are taken as a measure of the effect of interaction on percutaneous absorption. Js may be determined experimentally or calculated from the slope of a plot of flux against the ratio of concentration to solubility. The validity of the method was verified by penetration experiments through an inert polypropylene membrane. Data for benzocaine penetration through hairless mouse skin showed that, with water as standard, interaction effects were not significant when propylene glycol was the solvent. However, interaction resulted in a tenfold decrease in benzocaine permeability from solution in polyethylene glycol 400. INTRODUCTION One of the major factors influencing percutaneous absorption is the nature of the vehicle. A change in solvent character causes alteration in affinity of permeant for the solvent. As a result, partitioning into the membrane, and consequently, the transport rate are changed. An example is the dependence of permeability coefficient of a series of alkanols on carbon number (1). When the solvent was water, an increase in carbon number caused an increase in permeability coefficient. With isopropyl palmitate as solvent, the opposite trend was found. In each series, an increase in permeant affinity for the solvent resulted in a reduction in transport rate. The effect of solvent on partitioning of a permeant to the outer layer of the skin is a noninteractive influence because the properties of the barrier are not altered. It is also possible for solvents to interact with the stratum corneum so as to change its resistance to diffusion. The effect may be of an irreversible nature, in which damage to membrane integrity takes place, or it may be less drastic, involving solvent penetration followed by temporary alteration of barrier properties (2). The replacement of water molecules in the stratum corneum by those of another solvent can affect drug solubility, thereby influencing partitioning behavior. 327