A Consideration on Infinite and Finite Dosing in Skin Permeation Using Reconstructed Models

Abstract

Introduction: When vitamin derivatives penetrate the epidermis, they release active compound such as ascorbic acids (AsA) and tocopherols via enzymatic digestion of chemical modifiers. To determine the transdermal penetration of the derivatives, the total permeation of both the derivatives and their active compounds that released from the derivatives should be considered. In this study, we established a skin penetration test method using a cultured, reconstructed skin model with active epidermal enzymes. And we analyzed two vitamin derivatives with different chemical properties: magnesium ascorbyl phosphate (APM) and sodium tocopheryl phosphate (TPNa), both of which has been confirmed their skin permeation in the reconstructed models and the digestion to AsA and α-tocopherol by the epidermal enzymes, respectively. Methods: We prepared the 1% of water solution containing either APM or TPNa. Then, we tested the cumulative permeation of the derivatives at 2 application volumes, 25 μL/cm2 (finite dosing) and 85 μL/cm2 (infinite dosing), on cultured reconstructed skin and observed the permeation of the permeants every 2 h up to 24 h. Results: When the applied formula was used to assess the evaporation rate to determine an end point of the test system, all the water evaporated in 6 h in finite model and in 8 h in infinite model. Both models showed that the cumulative permeation of the active compounds increased and a constant flux until 8 h after application; however, the flux decreased thereafter, indicating that the decreased flux depended on an end point of the test system. This indicated that our test system can analyze the permeation of the vitamin derivatives within 8 h before reaching the end point. Conclusion: Using an infinite model of this system, we assessed the cumulative permeation of vitamin derivatives within 8 h using a reconstructed skin model.