EMULSION VEHICLES AND VASOCONSTRICTOR ACTIVITY 151 Formula 30 E • 25 • 20 ß t 0.06 zi 2. 0.19 x to o. :55 o t:5 1.:54 • 2:5 0.88 ß 6 1.:54 [] .17 0.57 ß :51 1.:54 [] 28 1.34 0 24 t.34 ß 19 J. 34 e 56 3.59 ( • =Oi[ / Water Phase-Volume Ratio) 0 15 :50 45 60 75 90 Time, minutes Figure 4. In vivo transepidermal water loss of the twelve selected hydrocortisone 17-valerate 0.2% o/w emulsions at ambient conditions (23 + 2øC, 40 -+ 5% RH). resulting data as shown in Figures 7 and 8. Figure 7 depicts the relationship between the permeability constant of formulas and a range of phase-volume ratios from O. 19 to 1.34. A positive linear trend found from the profile suggested that the permeability rate of HCV increased as the phase-volume ratio (4)) was increased. Formula #28 (4) = 1.34) has a permeability constant (Kp) of 5.71 X 10 -5 cm/hr, which is 2.4 times

152 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS FormuLa # .• ß 28 1 .•4 ß 1o o.•5 [] 2• 0.88 o 1 0.06 ß t7 0.57 A 2 0.19 (•: 0i[/Water Phase-VoLume Ratia) I 4 8 24 28 32 48 52 56 72 Time, hours Figure 5. In vitro human skin permeation profiles of the selected hydrocortisone 17-valerate 0.2% emul- sions with •b ranging from 0.19 to 1.34. The bar indicates the standard error of the means (n = 3). higher than that of formula #2 (qb = 0.19). Figure 8 demonstrates the relationship of the permeability constants of formulas with a constant phase-volume ratio (qb = 1.34) but different % levels of petrolatum. A positive linear trend suggested that the perme- ability constants of HCV increase as the concentration of petrolatum increases. This was not the case for mineral oil, where the permeability constants of HCV did not increase as the concentration of mineral oil increased. Formulas # 1 and #36, the two extremes, both showed low permeability rates as compared to other formulas. The drying effect due to the high volatility was considered to result in the low permeability rate of formula # 1 (2). High viscosity with low driving force in the high petrolatum vehicle, which might cause the HCV to have a tendency to stay in the hydrophobic phase, was presumably the cause of the low permeability of formula #36. IN VIVO VASOCONSTRICTOR ACTIVITY DETERMINATION All the experimental results from the above studies suggested that formula #28, which contains 28.9% water, 40% petrolatum, and 10% mineral oil, is the most desirable