PERCUTANEOUS ABSORPTION STATEMENT OF PROBLEM AND CRITICAL REVIEW OF PAST METHODS By IRv'if• H. B•,ANK* Presented September 23-2¾, 1959, Seminar, New York City IT SEEMS to me that the cosmetic chemist should continuously ask himself what he expects a cosmetic to accomplish and by what mechanism a given cosmetic may produce the desired results. I believe it is correct to say that the detailed mechanism of action of many cosmetics is unknown. Why do I bring up mechanism of action in a symposium on percutaneous absorption ? As most of you know, for several years I have been interested in emollients, and it is my contention that these substances can relieve a sensation of dryness without penetrating into the skin. In working with emollients it is, therefore, unnecessary to study the percutaneous absorp- tion of their ingredients in order to understand the way in which they function. But this is probably not true of many other types of cosmetics. Any antiperspirant capable of decreasing the activity of the sweat gland must penetrate into the skin and reach the gland. If a topically applied estrogen causes swelling of the collagen fibers, it must have penetrated and reached the dermis. Any cosmetic ingredient which has caused allergic sensitization must have penetrated the skin and reached the reticulo-endothelial system where antibodies are produced. It is entirely fitting, therefore, that the cosmetic chemists should be devoting a two-day seminar to the study of percutaneous absorption. In order to understand the way in which a cosmetic acts, it is usually helpful to know (a) whether any ingredient of that cosmetic can penetrate into the normal skin (b) how far into the skin it can penetrate, (c) with which specific tissues it comes in contact, and (d) the rate at which it penetrates. These, then, are some of the problems of percutaneous absorp- tion which confront the cosmetic chemists these are some of the questions which must be answered. As you know, and as you will hear in some detail during this symposium, percutaneous absorption has been studied in experimental animals and man * Dermatological Research Laboratories, Dept. of Dermatology, Harvard Medical School at the Massachusetts General Hospital, Boston 14, Mass. 59

60 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS it has also been studied in excised skin and in the intact skin of man and animals during life. The information obtained from these various types of investigation cannot be suitably interpreted until one knows whether data obtained from animals are applicable to man and whether data obtained from excised skin and from the intact skin of living man are comparable. We must keep these considerations continuously in mind. It is now no longer adequate to say simply that the skin is relatively impermeable to warm' because it is able to prevent dehydration of the body. We must not be satisfied with the vague statement that the skin is quite permeable to mustard gas, nerve gas and estrogens simply because we know that dramatic cutaneous or systemic reactions follow topical application of these subs•:ances to normal skin. It is, of course, true that absorption of mustard gas, a nerve gas or an estrogen from the cutaneous surface can be followed by vesicle formation, death of an experimental animal, or en- largement of mammary tissue, respectively--.reactions which are merely evidence that some absorption has taken place. These reactions do not in themselves measure the amount of absorption that has taken place they cannot serve, therefore, as the quantitative measure of permeability that we need for amplification of knowledge. I here deliberately used the words "absorption" and "penetration" interchangeably. It is not necessary in our discussion today to define these words with great precision, as is so often done in print, or to distinguish sharply between their meanings. Attempts to make such fine differentia- tions between terms may defeat the purpose of a symposium such as this. Todaywe are anxious to focus attention on themovement of molecules of var- ious substances into and through the skin, without attempting to establish minutely precise terminology. We want to know how many molecules move into the skin from a unit area of cutaneous surface in a unit of time, and where these molecules go after leaving the cutaneous surface. If we can consistently think in these terms, i.e., on the molecular level, it is not important whether we call this migration of molecules "absorption," "sorption, .... persorption, .... permeation, .... penetration" or any other name. As you have seen on the program, this morning's session is devoted to a discussion of the methods used for studying percutaneous absorption. Sound methodology is the foundation of any investigative work. We shall first consider whether the methods which have been used in studying percutaneous absorption are sound, if they give quantitative data concern- ing penetration of molecules, and if they indicate where these molecules go after they have left the surface of the skin. It is not my intent to present an all-inclusive review of percutaneous absorption. Several thorough reviews (1-3) have been published recently. Rather, I shall propose a classification of the various methods which have been used for the study of