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J. Soc. Cosmet. them., 39, 139-157 (1988) Effect of phase-volume ratio of o/w emulsion vehicles on the activity of a topically applied vasoconstrictor JONAS C. T. WANG, S. R. WINARNA, J. L. LICHTIN, and B. G. PATEL, Pharmaceutical Research & Development Division, Bristol-Myers Co., Buffalo, NY 14213 (J.C.T.W., B.G.P.), and College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267 (S.R.W.,J.L.L.). Received July 30, 1987. Synopsis This study was intended to test the relationships among phase-volume ratio, transepidermal water loss (TEWL) and skin permeation with the activity of vasoconstrictor emulsions containing hydrocortisone 17-valerate (HCV). Formulas with a phase-volume ratio of 3.59 provide the highest occlusivity (lower TEWL values), while formulas with phase-volume ratio of 0.06 or 0.19 were not occlusive. The major ingredient affecting occlusivity of the o/w emulsion systems is petrolatum, not mineral oil. In vivo vasocon- striction activity of a selected HCV 0.2% emulsion relative to several marketed intermediate or moderate corticosteroids was also assessed in 24 normal subjects. The results suggest that the vasoconstriction ac- tivity of the newly developed HCV 0.2% emulsion was greater than that of the HCV 0.2% cream, consis- tent with the in vitro skin permeation data. This study also reveals that the permeation rate of o/w emul- sions can be increased by increasing occlusivity while still maintaining the cosmetic elegance of o/w emul- sions. INTRODUCTION If a drug candidate intended for topical medication is to be a useful therapeutic agent, the active moiety must be formulated in a vehicle that is medically rational, physico- chemically stable, cosmetically acceptable to the patient, and, above all, able to en- hance the drug's biologic activity (1-3). It is known that the clinical efficacy of a topical medication is determined as much by its ability to reach the inflamed tissue as by its inherent activity and the characteristics of the molecule itself. Vehicle design plays a crucial role in the development of an active molecule. In fact, an inappropriate vehicle will diminish a drug's therapeutic potential. Conversely, a suitable base can significantly increase the penetration rate in skin and thereby improve the drug's bio- availability and activity (4,5). In theory, the ideal vehicle should act as an inert me- dium in which the drug is incorporated in a homogeneous phase. In this study hydrocortisone 17-valerate (HCV), a nonhalogenated derivative of hydro- cortisone shown by Cornell and Stoughton (6) in their clinical evaluation and vasocon- strictor assay to be a mid-potent steroid with superior biological activity over its parent compound, was selected as the candidate molecule. Hydrocortisone 17-valerate 0.2% 139