74 JOURNAL OF COSMETIC SCIENCE N ,:, E 40 ·u CJ 35 C) .!:! :::s C .!:! .:: 20 .... en - 15 Cl) 10 Cl) 5 0 Epidermis 0% 1% 3% Dermis Polymer Dose Receptor * All formulations contained 2% salicylic acid (table IA). Penetration in receptor was measured at 24 hours. -0% is formula I and is the nonionic isoceteth-20 hydroalcoholic formula with 0% polymer -1 % is formula 2 and is the nonionic i soceteth-20 hydroalcoholic formula with 1 % polymer -3% is formula 4 and is the nonionic isoceteth-20 hydroalcoholic formula with 3% polymer Figure 3. Salicylic acid penetration into the epidermis, dermis, and receptor from isoceteth-20 formula­ tions: Effect of polymer dose. Table III Ratio of Salicylic Acid in the Receptor to That in the Epidermis at 24 Hours in Various Hydroalcoholic Formulations Formulation* Reference 2% SA anionic formula (no polymer) Isoceteth-20 prototype with 0% polymer lsoceteth-20 prototype with 2% polymer lsoceteth-20 prototype with 3% polymer Ratio of salicylic acid:receptor/epidermis 2.3 1.45 1.1 0.8 * All formulations contained 2% salicylic acid and are shown in Table IA. Penetration was measured for 24 hours. Anionic formula is shown in Table IA. Formula 1 is the nonionic isoceteth-20 system with 0% polymer. Formula 3 is the nonionic isoceteth-20 system with 2% polymer. Formula 4 is the nonionic isoceteth-20 system with 3% polymer. salicylic acid in a sodium lauryl sulfate anionic surfactant system without the polymer than from the same formulation (formula 8) with 3% polymer (formulations in Table IA). Thus the polymer effect does not seem to depend on the surfactant in the system. We also looked at the influence of three formulation ingredients in the nonionic hy­ droalcoholic system on the penetration of salicylic acid into various layers of the skin. The three ingredient variables were the nonionic surfactant, isoceteth-20 polyolpre­ polymer and the pH adjuster, triethanolamine (TEA). Figure 5 (and Table II, experi­ ment one) shows that formulation 4 performed the best at minimizing the penetration
N c .2 TARGETED DELIVERY OF SALICYLIC ACID 70 60 50 40 30 20 10 0 anionic 3% polymer Formulations Epidermis ■Dermis □Receptor * A]] fonnu]ations contained 2% sa]icy]ic acid (table 1 A). Penetration was measured at 24 hours. -Anionic is reference sodium lauryl su]fate hydroa1coho]ic anionic formulation with 0% po]ymer 75 -3% polymer is formula 8 and is the sodium Jaury] su]fate hydroalcoho]ic formulation with 3% polymer Figure 4. Penetration of salicylic acid from anionic surfactant formulations with and without polymer into the epidermis, dermis, and receptor: Effect of polymer. rate of salicylic acid into the receptor and maximizing entrapment of the drug in the epidermis [it was significantly better than all other formulations at achieving this (p 0.05)}. Three ingredients must be present to achieve this, namely isoceteth-20 surfac­ tant, TEA, and an optimized amount of polymer (3% in this case). If any of these are deleted, such as in formulas 1 (polymer deleted), 5 (TEA deleted), 6 (isoceteth-20 deleted), and 7 (polymer and isoceteth deleted), significantly more drug goes into the receptor and less into the epidermis (p 0.05). Thus there is a synergistic-type of relationship between these three components to target drug delivery into the epidermis and slow release into the receptor and hence through the skin. We also compared drug penetration from the 0. 5 % salicylic acid prototype nonionic formulations (see Figure 6) with or without the polymer and from an anionic formula­ tion containing 0.5% salicylic acid. Results for these low salicylic acid formulations continue to show that the polymer slows delivery of the drug through the skin (although in this case the 1 % polymer effect did not quite reach statistical significance) and that the nonionic system in general is significantly better at slowing delivery of the drug through the skin than the anionic formulation (p 0.05 ). The anionic system was not .sodium lauryl sulfate in this case rather, it was lauryol sarcosinate and lauryl sulfosuc­ cinate. Still, the nonionic system surpassed the alternate anionic system in slowing delivery of salicylic acid into the skin. IN VIVO CLINICAL PATCH TEST RESULTS In order to determine if the polymer effect of reducing penetration of salicylic acid through the skin results in reduced irritation, we tested isoceteth-20 formulations with different levels of polymer versus no polymer versus current marketed reference formu-
Previous Page Next Page