190 JOURNAL OF COSMETIC SCIENCE Results: The experimental data are shown in Table 1. Evaporation rate increased in direct proportion to airflow. The percent of dose evaporated after 24 h ranged from 16 ± 4 % at v = 10 mL/rnin to 53 ± 7% at v = 80 mL/rnin. Absorption and evaporation rates of DEET at selected airflows are depicted in Figure 2. Table 1: Mass balance of 1 ¾w/w solution of 14 C-DEET from human skin in vitro as a percent of dose rd1e app % Dose evaporated % Dose absorbed Total Airflow Para film Recovery mL/rnin Cartridge • Et-OH bTissue Receptor Rinsing Fluid IO 15.8±3.8 1.2±0.3 8.0±2.9 68.8±6.6 0.7±0.5 94.5±1.1 20 29.1±5.5 1.4±0.3 7.4±0.6 51.8±6.0 0.0±0.0 89.7±5.1 30 41.3±10.5 1.9±0.4 11.9±4.0 36.7±9.7 0.4±0.2 92.2±4.0 40 42.4±3.6 0.6±0.l 5.9±1.0 32.0±1.4 0.0±0.0 81.0±3.9 50 51.1± 14.8 1.4±0.3 13.5±8.3 24.7±6.1 0.0±0.0 90.8±7.0 60 44.9±3.0 0.9±0.2 5.8±1.l 26.5±3.1 0.0±0.0 78.1±1.2 70 58.8±6.7 0.8±0.3 11.3±8.2 20.0±2.6 0.4±0.3 92.0±1.0 80 52.4±7.3 0.7±0.l 13.4±6.l 19.7±1.3 0.8±0.5 87.0±3.6 100 37.6±10.6 0.5±0.2 13.6±9.2 21.6±6.6 1.9±1.8 89.2±3.7 a - (II) - Ethanol rmsmg of evaporation trap, modified Franz cell top and connecting tubes (where applicable), b =%dose recovered from skin and Para film (where applicable) at end of experiment, i.e, 24/25 hrs. Figure 2: 14C-DEET evaporation and absorption rates from human skin in vitro as a function of airflow over the diffusion cell. (E) = Experimental values, (T) = Theoretical Prediction x 12 10 6 6 4 2 0 -2 ◊ ◊ ■ • I 0 ABSORPTION EVAPORATION • 20 ml/min (E) 'iJ 40 ml/min (E) ◊ ■ 70 ml/min (E) 60 ml/min (E) 20 ml/min (T) 40 ml/min (T) 70 ml/min (T) 60 ml/min (T) 5 10 15 20 0 5 10 15 Hours, post dose Hours, post dose 20 Conclusion: Evaporation and absorption of solvent deposited volatile compounds from skin can be satisfactorily described by a diffusion model employing accessible physical properties and a simple representation of the skin barrier. References: 1. Arjun Santhanam, Matthew A. Miller and Gerald B. Kasting, Toxicology and Applied Pharmacology, 204, 81-90 (2005). 2. Matthew A. Miller, Varsha Bhatt and Gerald B. Kasting, J. Pharm. Sci, in press.

2005 ANNUAL SCIENTIFIC MEETING 191 FORMULATING FOR FAST EFFICACY Johann W. Wiechers1, Ph.D., Caroline L. Kelley2, Ph.D., Trevor G. Blease2, Ph.D. and J. Chris Dederen3, Ph.D Introduction: Uniqema Applied Research, 1 The Netherlands Uniqema Applied Research, 2 United Kingdom Uniqema Applied Research, 1 Belgium SOlulliHty penelrant\ The underlying issue in not delivering the promise of cosmetic products in a consumer-noticeable and fast way is very often the lack of sufficient skin delivery of active ingredients into the skin. Our previous work has indicated that the choice of the emollients determines the quantity of active ingredient penetrating the skin. The polarity of the phase in which the active ingredient is solubilized can be calculated and is a compromise between the solubility of the active ingredient in the formulation on the one hand and the driving force for penetration into the skin on the other hand. For details of this so-called Formulating for Efficacy concept, see Figure 1 and ref. l. -s1l penelnlnl I l110l'fJ hydrophilic -PPG polarity + PPG penetrant more lipophilic Figure 1: Schematic representation of the "Formulating for Efficacy" Co11cept Whereas this approach helps to increase the quantity of active ingredient penetrating the skin, it does not guarantee that at any given time, there is also sufficient active ingredient at the site of action to achieve levels above the minimal effective concentration. To achieve this, the deposition of active ingredient in skin - the so-called drug targeting - should also be taken into account. Deposition of ingredients is influenced by both the rate and extent of the percutaneous absorption process. Whereas the choice of emollients regulates the extent to which active ingredients penetrate the skin, the choice of the emulsifier influences the rate of skin penetration, probably due to the interaction of enmlsifiers with skin lipids. In order to investigate the influence of emulsifiers on the rate and extent of skin penetration of cosmetically active ingredients, two types of studies were performed: 1. Clinical studies in which the emollient was used as the active ingredient (either acting as a skin moisturizer or as a skin elasticity provider both emollients were lipophilic) 2. Skin penetration studies in which a hydrophilic or a 1ipophilic active ingredient were included in formulations using emulsifiers that formed either liquid-crystalline emulsions or not. Results: In the clinical trials in which 36 formulations were tested for either skin moisturization ( 18 formulations 9 containing a good moisturizing emollient and another 9 containing a poorly moisturizing emollient) or skin elasticity (another 18 formulations also 9 with a good elasticity-providing emollient and another 9 with a poor elasticity-providing emollient). All formulations were applied for 6 hours. Formulations with a liquid-crystalline structure gave better skin moisturization or skin elasticity as measured by the Comeometer or Dermal Torque meter, respectively (see Figure 2). From this, we concluded that these formulations deliver more of the lipophilic moisturizer or elasticity-provider into the (epi)dermal layers of the stratum comeum at 6 hours. Figure 1: (Epi)deNlf#I hlivery (ond tJ,us moisturization) is better from lifuid-crystallineforWJulations. In the skin delivery studies, the total skin penetration of the lipophilic octadecenedioic acid was the same after 24 hours from a liquid-crystalline and a non-liquid crystalline formulation. However, while the dennal delivery was high and the transdermal delivery low from the non-liquid crystalline formulation, this was reversed for liquid-crystalline fomrulation, suggesting the skin penetration of lipophilic ingredients to be faster from liquid crystalline systems (see Figure 3). In contrast, the total skin penetration of the hydrophilic propagermanium increased significantly from a liquid-crysta1line fonnulation but the transdermal delivery was low from both formulations types. From this, we conclude that the skin