244 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS show how topobiological interactions can alter tissue pattern and animal form, and comment upon some possible applications of these findings. SCIENTIFIC SESSION C (Concurrent) PRODUCT EVALUATION Clinical evaluation of cosmetic products: A cri- tique of current concepts Morton Pader, Ph.D., Consumer Products Devel- opment Resources, Inc., 1358 Sussex Road, Teaneck, NJ 07666 The design and interpretation of clinical trials of cosmetic products are explored. A valid assessment of the efficacy of a new product must take into ac- count at least two major concerns: (1) the nature of the placebo or control and (2) compliance of the subject with predetermined product dosage. The first concern involves overcoming the Hawthorne effect in the clinical design. This is usually at- tempted by the use of a placebo, but the approach is not always sound, as demonstrated by examination of pertinent reports to be cited from the literature. Compliance with product usage is rarely accommo- dated in clinical trial design. A review of published studies suggests clinical trials can be usefully con- sidered in three categories for evaluation of product efficacy. These encompass a hierarchy of designs ranging from testing of product and elements thereof in simple, well-established vehicles and evaluation systems, through field trials which bring into play the factor of compliance. Examples from the literature and practice are given to illustrate features of three types of clinical trial and the role of each in complete product evaluation. Negative aspects of some currently favored clinical designs are critiqued based on these examples. Combined application of topographical and light reflectance methods for evaluation of skin condition Peter L. Dorogi, Ph.D., Peter R. Hilliard, Jr., Ph.D., Alfred A. Hambidge, Jr., and June T. Hull, Clairol, Inc., Clairol Research Laboratory, 2 Blachley Road, Stamford, CT 06922 Short-term exposure of skin to cold hexane induces a clearly visible "ashy" condition, similar to that seen in severely dry skin conditions. Detailed mi- croscopic examination of the skin surface, using scanning electron microscopy (SEM) and high-reso- lution profilometry, reveals the prevalence of loose scales and a relatively flat surface relief, and shows that the perceptible ashiness induced by hexane is due to both surface damage and dehydration. An investigation was conducted to see whether the re- sponse to hexane can be used as a predictive tool to test the tendency to develop dry skin symptoms. The appearance of dryness was assessed objectively using tristimulus parameters (L,a,b) to describe re- flectance properties of the skin. Measurements were obtained on 15 subjects before and after hexane ex- posure, during both summer and winter. Results include the finding that total reflectance (L) is more dramatically affected in winter than summer (p 0.001), and suggest the possibility of using hexane-enhanced light refectance from the skin for objective assessments of the susceptibility to dry- ness. Consumer-driven product development-- Creating winning products by putting con- sumers into the development loop Howard R. Moskowitz, Ph.D., Moskowitz/Jacobs, Inc., 14 Madison Avenue, Valhalla, NY 10595 The competitive marketplace measures success by consumer purchase and repeat rate. This presenta- tion shows how the product developer and marketer can use consumer responses to create products that are more acceptable, less costly (in ingredient dollars), and more targeted to specific groups of consumers. The approaches use structured develop- ment of concepts to create positionings, segmenta- tion of consumers to find ready niches of consumers interested in the product, and systematic product development and optimization to create the actual products satisfying those niches of consumers. Applications and pitfalls of in vitro release and skin penetration studies Joel L. Zatz, Ph.D., Rutgers University, P.O. Box. 789, Piscataway, NJ 08855-0789 During product development, measurements of skin penetration in vitro provide one means of com- paring candidate formulations. The rationale for using excised human skin is that the principal skin barrier, the stratum corneum, is already dead and will therefore not suffer by removal from the live organism. Among the potential limitations of in vitro experiments are the loss of enzymatic activity and development of diffusional resistance within the aqueous skin layers. The seriousness of each of these problems, and strategies for dealing with them, de- pend largely on the chemistry of the permeant. Al- though excised human skin is often preferred for in vitro studies, a high degree of skin variability may cloud comparisons made among competing formu- lations. Selection of appropriate experimental con- trols helps to alleviate this problem. Under certain conditions, release from the vehicle may become

ABSTRACTS 245 rate-limiting. Release experiments may then pro- vide insight into the permeation process. SCIENTIFIC SESSION D (Concurrent) GENERAL PAPERS Inhibition of UVB-induced arachidonic acid release in vitro as a model for evaluation of anti-inflammatory ingredients K. Marenus, Ph.D., T. Mammone, S. Jadlos, D. Maes, and W. Smith, Estee Lauder Co., Research Park, 125 Pinelawn Road, Melville, NY 11747 The release of arachidonic acid from the cell mem- brane is the committing step to the prostaglandin cascade. Prostaglandins have been shown to mediate inflammation in vivo. We have investigated UVB- induced arachidonic acid release as a model of in- flammation. Prior to testing, materials were evalu- ated for cellular toxicity, and acceptable use levels were determined. Normal human keratinocytes were prelabeled for 24 hours with tritiated arachi- donic acid. These cells were then irradiated with 0, 400, 800, and 1200 mJ/cm 2 UVB. These doses caused a graded release of arachidonic acid and therefore can be used as a model for inflammation. Several agents were found to inhibit arachidonic acid release (Table). This in vitro model is useful for screening prospective ingredients. Table Average reduction Anti-inflammatory Conc. (across all doses) Ibuprofen 0.02 33 % Indomethacin 0. 325 26% Cortisone 0.05 24% Acetyl salicylate 0.03 2 ! % Effects of enhancer pretreatment in skin per- meation of erythromycin M. S. Kislalioglu, Ph.D., and A. Iyer, Department of Pharmaceutics, University of Rhode Island, Kingston, RI 02881-0809 In this study, the effects of propylene glycol (PG), oleic acid, and Azone pretreatments on the skin up- take and on the flux of erythromycin from saturated pH 8.9 borate buffer (BP) and isopropyl myristate (IPM) solutions were investigated. The left dorsal back skins of hairless mice having 2.5 cm 2 areas were treated with 10 pA of the enhancer. Right dorsal back sides were used as controls. The animals were sacrificed after an hour, and the pretreated skins and control sites were removed and placed in the Franz cells. Saturated erythromycin solutions (100 pA) were then spread on the skin pieces, and diffusion of •4C-labeled erythromycin was followed by liquid scintillation counting. PG treatment had no effect on the flux of erythromycin from BP and from IPM. It exerted no changes in skin concentra- tions. hzone pretreatment caused a more pro- nounced increase in erythromycin diffusion from IPM than from BP. Azone was the most potent en- hancer in increasing the flux of erythromycin. Phospholipid liposome/surfactant interactions as predictors of skin irritation Ursula K. Charaf and Gerald L. Hart, S. C. Johnson Wax, 1525 Howe Street, Racine, WI 53403 A sensitive method is described where large unila- mellar liposomes are used as a model membrane system to study and define surfactant-skin interac- tions. The relative tendency of surfactants or surfac- tant blends to form mixed micelies with liposome membrane components determines the aggressivity factor believed to be related to in vivo surfactant irri- tation responses. Single surfactants and surfactant mixtures were investigated, and their behavior to- ward liposome membranes was used to establish a mathematical index of surfactant aggressivity. Good correlation was established between this index and in vivo scores for the anionic surfactants and blends tested, as well for as some types of nonionics and mixed blends. This method has distinct advan- tages over traditional in vivo tests. It is expedient, inexpensive, sensitive, objective, and reproducible. Moreover, it does not use live animals and does not derive its components from tissues or organs. In vitro permeation of tolmetin through irra- diated and non-irradiated hairless mouse skin Jean P. Holland, R.Ph., and E. R. Lukenbach, Ph.D., Johnson &Johnson Baby Products Co., 199 Grandview Road, Skillman, NJ 08558, and J. L. Lichtin, M.D., and A. Sakr, Ph.D., University of Cincinnati, Cincinnati, OH Over exposure of the skin to ultraviolet radiation, sunburn, will result in redness, swelling, heat, and pain. Currently marketed sunburn treatment products are only palliative. The literature indicates that topical non-steroidal anti-inflammatory agents exhibit a potential to be a therapeutic treatment. This study explores the effect of ionization of a non- steroidal anti-inflammatory agent, tolmetin, on permeation and explores the effect of skin irradia- tion on in vitro permeation. Five solutions ranging from 0.99 to 99.30% ion- ized were applied to irradiated and non-irradiated albino hairless mouse skin in Franz diffusion cells.