TARGETED DELIVERY OF SALICYLIC ACID 69 PENETRATION STUDIES A study (Figure 1) was run with 2% salicylic acid formulations containing a hydroal­ coholic, nonionic (isoceteth-20) surfactant system (formulations in Table IA) to examine the effect of polymer dose on penetration of salicylic acid from the formulation. In that study we also compared the salicylic acid penetration from the prototype nonionic surfactant formulations with and without the polymer with an anionic surfactant for­ mulation to provide insights into the effect of the surfactants used in salicylic acid penetration. This experiment showed that addition of the polymer to the prototype nonionic system reduced the rate of delivery of the drug through the skin to the receptor fluid over the time period tested (see penetration profiles for prototypes containing 0%, 2%, and 3% polymer in Figure 1). In fact, the 0% polymer formulation delivered a significantly higher (p 0.05) amount of drug through the skin to the receptor over the 24-hour time period than the 3% polymer-containing formulations (Table II, experi­ ment two), and the 2% polymer-containing formulations delivered an amount of SA between the two. Results again confirm previous findings (12) that the addition of the 60 Anionic 0% Anionic 50 2% N �3% E 40 �Nonionic C 30 0 G 20 C G 10 0 0 6 12 18 24 Incubation time, hours *All formulations contained 2% Salicylic Acid and are displayed in table IA. Penetration was measured at 24 hours. -Anionic is a sodium lauryl sulfate anionic hydroalcoholic reference formulation without polymer -0% - Formula 1 is a nonionic lsoceteth-20 hydroalcoholic system with 0% polymer -2% - Formula 3 is a nonionic Isoceteth-20 hydroalcoholic system with 2% polymer -3% - Formula 4 is a nonionic Isoceteth-20 hydroalcoholic system with 3% polymer -Nonionic is a reference nonionic hydroalcoholic formulation also containing Isoceteth-20 (no formula analysis available) Figure I. Penetration of salicylic acid from nonionic vs anionic formulas through skin: Effect of polymer dose.

Table IA Composition of 2.0% Salicylic Acid Formulations Tested Reference Reference anionic nonionic Component formula formula Formula 1 Formula 2 Formula 3 Formula 4 Percentage of component Ethyl alcohol, 200 proof 42 * 42 42 42 42 Salicylic acid 2.0 2.0 2.0 2.0 2.0 2.0 Sodium lauryl sulfate 0.2 Isoceteth-20 * 0.9 0.9 0.9 0.9 Polyol prepolymer-15 1.0 2.0 3.0 Propylene glycol 0.8 Polyethylene glycol 0.8 EDTA tetrasodium salt (36%) * 0.05 0.05 0.05 0.05 T riethanolamine * 0.1 0.1 0.1 0.1 Glycerine 5.0 Citric acid 0.3 Water QS QS QS QS QS * Exact amount is unknown. Formula 5 Formula 6 Formula 7 42 42 42 2.0 2.0 2.0 0.9 3.0 3.0 0.05 0.05 0.05 0.1 0.1 QS QS QS Formula 8 42 2.0 0.2 3.0 0.8 0.8 5.0 0.3 QS ----..J 0 0 C z 0 n 0 C/'J tTJ - n C/'J n - z n tTJ