Stratum corneum reservoir as a predictive method for in vitro percutaneous absorption

• Published in: Journal of applied toxicology Vol. 36; no. 8; pp. 1003 - 1010
• Main Authors: Hafeez, Farhaan, Chiang, Audris, Hui, Xiaoying, Zhu, Hanjiang, Kamili, Faraz, Maibach, Howard I.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.08.2016; Wiley Subscription Services, Inc
• Subjects: Benzylamines - pharmacokinetics; Cadaver; Epidermis - drug effects; Epidermis - metabolism; human; Humans; in vitro; Ketoconazole - pharmacokinetics; Kinetics; Linear Models; Naphthalenes - pharmacokinetics; penetration; percutaneous absorption; Pharmacology; Pyridones - pharmacokinetics; skin; Skin - drug effects; Skin - metabolism; Skin Absorption - drug effects; stratum corneum; Toxicology; skin; stratum corneum; percutaneous absorption; penetration; human; in vitro
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3262

Interaction between drug and proteins and lipids in stratum corneum (SC) is an important pharmacokinetic parameter in early steps of absorption. Previous in vivo studies showed that the total amount of compound, regardless of properties, penetrating over a 96 h period could be predicted by the amount present in SC 30 min after application by a linear relationship. Validating this linear relationship through in vitro study would facilitate testing of transdermal drug delivery platforms. We aimed to determine in vitro penetration behavior across SC of humans by determining the relationship between quantity present in SC reservoir 30 min after application with 24 h skin absorption and penetration. In this study, use of the SC reservoir effect to predict absorption and penetration of topical compounds is reaffirmed with in vitro models involving human skin. These results indicate the amount in short‐term (30 min) SC reservoir predict long‐term (24 h) skin absorption and penetration, as characterized by statistically significant linear relationships determined via regression. This may be explained by the fact that SC is a rate‐limiting barrier to percutaneous drug transport. After molecules diffuse through SC barrier, passage into deeper dermal layers and systemic uptake occur relatively quickly. These results enable one to measure quantity in SC reservoir shortly after topical application as a proxy for absorption and penetration over longer periods. With respect to drug development and risk assessment of toxic substances, this may simplify assays attempting to quantitate penetration capacity. Further investigation with a larger range of compounds is needed to clarify the observations recorded here. Copyright © 2015 John Wiley & Sons, Ltd. Interaction between drug and stratum corneum (SC) is an important pharmacokinetic parameter in absorption. Previous in vivo studies showed the amount penetrating over a 96 h period could be predicted based on the linear relationship with the amount in SC after a 30 min application. We aimed to determine in vitro penetration behavior across SC by determining the association between quantity in SC 30 min after application and penetration after 24 h. Linear relationships are shown between quantity in SC 30 min after application and penetration after 24 h.