CORTICOID, VEHICLE, AND SKIN INTERACTION 589 concern if this presentation were made a few years ago. Although all are important factors which must be considered, they are certainly secondary to the primary goal of achieving optimal therapeutic efficacy. Attention has been directed to the interaction of the basic triad of components (corticoid, vehicle, and skin), their resultants (release, penetration, and interaction), and their cuhnination in a highly effective therapeutically active product. (Received December 13, 1971) REFERENCES (1) Vickers, C. F. H., Corticosteroids, Practitioner, 21/2, 43-51 (1969). (2) Doffman, R. I., Biological activity of topical corticoids, Brit. J. Dermalol., 82, Supp. 6, 45-8 (1970). (3) Lerner, L. J., Bianchi, A., Turkhcimer, A. R., Singer, F. M. and Borman, A., Anti-in- flammatory steroids: Potency, duration and modification of activities, Ann. N.Y. Acad. Sci., 116, 1071-7 (1964). (4) Ringlet, A., Activities of Adrenocorticosteroids in Experimental Animals and Man, in Dorfman, R. I., Methods in Hormone Research, Academic Press, New York, Vol. •1, 1964 pp. 234-80. (5) Berlincr, D., Biotransformation of corticostcroids as related to inflammation, Ann. N.Y. •Icad. Sci., 116, 1078-83 (1964). (6) Berliner, D., Gallegos, A. J., and Schneebeli. G. L., Early morphological changes pro- duced by anti-inflammatory steroids on tissue culture fibroblasts, J. Invest. Dermatol., 48, 44-9 (I•67). (7) Ruhmann, A. G., and Berliner, D. L., Effect of steroids on growth of mouse fibroblasts in vitro, Enctocrinology, 76, 916-27 (1965). (8) McKenzie, A. W., Percutaneous absorption of steroids, Arch. Dermatol., 86, 611-3 (1962). (9) McKenzie, A. W., and Stoughton, R. B., Method for comparing percutaneous absorption of steroids, Ibid., 86, 608-10 (1962). (10) Place, V. A., Burdick, K. H., and Giner Velazquez, J., Precise evaluation of topically ap- plied corticosteroid potency, Ibid., 101, 531-7 (1970). (11) Stoughton, R. B., Vasoconstrictor activity and percutaneous absorption ooe glucoeorti- costerolds, a direct comparison, Ibid., 99, 753-6 (1969). (12) Tregear, R. T., Physical Functions of Skin, Academic Press, Inc., New York, 1966. (13) Stougbton, R. B., Dimethyl sulfoxide induction of asteroid reservoir in human skin, Arch. Dermatol., 91,657-60 (1965). (14) Katz, M., and Poulsen, B. J., Absorption of Drugs Through the Skin, in Brodie, B., and Gillette, J., Handbook of Experimental Pharmacology, 28/1, Springer-Verlag, Berlin, 1971, pp. 104-62. (15) Faber, L., unpublished data, 1970. (16) Higuchi, T., Physical chemical analysis of percutaneous absorption process from creams and ointments, ]. Soc. Cosmet. Chem., 11, 85-97 (1960). (17) Scheuplein, R. J., Blank, I. H., Brauner, G. J., and MacFarlane, D. J., Percutaneous ab- sorption of steroids, ]. Invest. Dermatol., 52, 63-70 (1969). (18) Ostrenga, J. O., Significance of vehicle composition. I. Relationship between topical vehicle composition, skin penetrability, and clinical efficacy, ]. Pharm. Sci., 60, 1175-9 (1971).

590 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (19) Katz, M., and Shaikh, Z., Percutaneous corticosteroid absorption correlated to partition coefficient, Ibid., 54, 591-4 (1965). (20) Scheuplcin, R. J., Mechanism of percutaneous absorption. I. Routes of penetratioa and the influence ooe solubility, J. Invest. Dermatol., 45, 334-46 (1965). (21) Poulsen, B. J., Young, E., Coquilla, V., and Katz, M., Effect ooe topical vehicle composition on the in vitro release of fluocinolone acetonide and its acetate ester, J. Pbarra. Sci., 57• 928-33 (1968). (22) Coldman, M. F., Poulsen, B. J., and Higuchi, T., Enhancement ooe percutaneous absorp- tion by the use of volatile:nonvolatile systems as vehicles, Ibid., 58, 1098-102 (1969). (23) Moore-Robinson, M., and Christie, G., Vasoconstrictor activity of topical corticosteroids. Methodology and results, Brit. J. Dermatol., 82, Supp. 6, 86-92 (1970). (24) Wagner, J. G., Biopharmacet•tics: Absorption aspects, J. Pharm. Sci., 50, 359-87 (1961). (25) Barrett, C. W., Hadgraft, J. W., Caron, G. A., and Sarkany, I., The effect of particle size and vehicle on the percutaneous absorption ooe fluocinolone acetonide, Brit. J. Dermato!., 77, 576-8 (1965). (26) Haleblian, J., and McCrone, W., Pharmaceutical applications ooe polymorphism, ]. Pharm. Sci., 58, 911-29 (1969). (27) Ostrenga, J., Steinmetz, C., Poulsen, B., and Yett, S., Significance of vehicle composition. II. Prediction ooe optimal vehicle composition, Ibid., 60, 1180-3 (1971). (28) Idson, B., Dry skin and emolliency, I, II, III, Drug Cosmet. Ind., 104, 105, June, p. 44 July, p. 48 Aug. p. 48 (1969). (29) Smeenk, G., and Rijnbeek, A.M., The water-binding properties of the water-soluble substances in the horny layer, Acta Dermato-Venereol., 49, 476-80 (1969). (30) Powers, D. H., and Fox, C., The effect of cosmetic emulsions on the stratum corneum, J. Soc. Cosmet. Chem., 10, 109-16 (1959). (31) Wurster, D. E., Factors Influencing the Design and Formulation of Dermatological Preparations, in Goldstein, S. W., Development of Safer and More Effective Drugs, Amer- ican Pharmaceutical Association, Washington, D.C., 1968, pp. 121-40. (32) Scholtz, J. R., Topical therapy of psoriasis with fluocinolone acetonide, Arch. Dermato!., s4, 191-2 (1961). (33) Kligman, A.M., Topical pharmacology and toxicology of dimethyl sulfoxide, Part I, J. Amer. Med. Ass., 198, 140-8 Part II, Ibid, 151-6 (1965). (34) Schumacher, G. E., Some properties of dimethyl sulfoxide in man, Drug Intel., I, 188-94 (1967). (35) Ostrenga, J. O., Haleblian, J., Poulsen, B., Forroll, B., Mueller, N., and Shastri, S., Ve- hicle design for a new topical steroid, fluocinolide, J. Invest. Dermatol., 56, 392-9 (1971). (36) Katz, M., and Neiman, H. M., U.S. Patent 3,592,930 (|uly 13, 1971). (37) Scholtz, J. R., and Dumas, K. J., Standards for Clinical Evaluation o• Topical Steroids, in XIII Congressus Internationalis Dermatologiae, Munchen, 1967, Springer-Verlag, New York, 1968. (38) Mendelson, C. G., and Bessler, S. A., Clinical efficacy of fluocinonide, a new topical corticoid, Cutis, 8, 557-80 (1971) and Spccial C•mmunication 9, 104 (19-2). (39) Milne, J. A., Clinical sequential trials in dern'a•ology, Brit. J. Dermalol., 82, Supp. 6, 99-•03 (1970). (40) Burdick, K. H., Corticosteroid bioavailability assays, Arch. Dermatol. (Stockholm), Suppl. 67 (1971), Fluocinonide International Symposium, Zurich, May 1971.