Koji Kawahara1, Kakuji Tojo. 1. Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4, Kawazu, Iizuka, Fukuoka, 820-8502, Japan. kawahara@nichiban.co.jp
Abstract
PURPOSE: Active pharmaceutical ingredients (API) in transdermal drug delivery systems (TDS) often causes skin irritation such as erythema and edema. We have studied a possible approach for the reduction of skin irritation by patch formulations that control the rates of skin permeation and elimination of API. METHODS: Loxoprofen (LX-base) was used to induce the skin irritation. The redness value (Deltaa) was evaluated as a measure of erythema by Chroma Meter. The in vitro skin permeation and release profiles were also investigated by using a side-by-side diffusion cell. RESULTS: The redness values were not correlated either with the cumulative amount of API permeated or the concentration of LX-base in the skin, but well correlated with the elimination rate of LX-base from the skin after the removal of the formulation. The formulation with gradual decrease of permeation rate during application accelerated the elimination rate after application, and resulted in the reduction of the skin irritation. CONCLUSIONS: The skin pharmacokinetics of API, not only permeation during application but also release after the patch removal, was found to be a significant factor for skin irritation. To minimize the skin irritation, it's also important to eliminate the residual API in the skin promptly after application.
PURPOSE: Active pharmaceutical ingredients (API) in transdermal drug delivery systems (TDS) often causes skin irritation such as erythema and edema. We have studied a possible approach for the reduction of skin irritation by patch formulations that control the rates of skin permeation and elimination of API. METHODS:Loxoprofen (LX-base) was used to induce the skin irritation. The redness value (Deltaa) was evaluated as a measure of erythema by Chroma Meter. The in vitro skin permeation and release profiles were also investigated by using a side-by-side diffusion cell. RESULTS: The redness values were not correlated either with the cumulative amount of API permeated or the concentration of LX-base in the skin, but well correlated with the elimination rate of LX-base from the skin after the removal of the formulation. The formulation with gradual decrease of permeation rate during application accelerated the elimination rate after application, and resulted in the reduction of the skin irritation. CONCLUSIONS: The skin pharmacokinetics of API, not only permeation during application but also release after the patch removal, was found to be a significant factor for skin irritation. To minimize the skin irritation, it's also important to eliminate the residual API in the skin promptly after application.