Effects of the Physicochemical Properties of Oil Vehicles on the Skin Penetration of Poor Skin-Penetrable Materials under Finite Dose Conditions In Vitro

Abstract

The topical delivery of active ingredients is based on partition and diffusion into the skin; the penetration of active ingredients into the skin depends on their partition coeffi cient (P) and molecular weight. In general, chemical compounds that have high or low P values or a molecular weight over 500 Da are poorly absorbed through the skin1–3). Therefore, drugs used as transdermal therapeutic systems must have appropriate P values (log P=1–3) and low molecular weight (<500 Da) 4). The evaluation of the skin penetration or absorption of these drugs has been performed under infinite conditions in many cases, because this approach facilitates theoretical analyses. However, often, topical agents and cosmetics are used in small amounts, which represent fi nite dosing. There is a possibility that fi nite dosing will change the donor concentration of active ingredients during experiments. One report has addressed the diffi culties of performing measurements and predictions based on fi nite dose conditions5). However, several trials have predicted the behaviors of chemical compounds in these conditions6–8). The OECD Test Guideline 428 also indicates the application of test substances at a concentration of up to 10 mL/cm2; in most cases, this application amount represents a fi nite dose condition9). Active ingredients with characteristics that are inappropriate for skin penetration (e.g., with a high molecular weight and high or low lipophilicity) are often used in skin therapeutics and cosmetics. J. Pharm. Sci. Technol., Jpn., 74 (1), 84-92 (2014)