In Vitro Human Skin Absorption of Solvent-deposited Solids: Niacinamide and Methyl Nicotinate

Abstract

A quantitative understanding of the dose dependence of topical delivery is important to cosmetic and dermatological product development and to risk assessment for hazardous chemicals contacting the skin. Despite considerable research, predictive capability in this area remains limited. To this end we conducted an experimental skin absorption study of two closely related skin care agents, niacinamide (nicotinamide, NA) and methyl nicotinate (MN), and analyzed the results quantitatively using a transient diffusion model described separately (Yu et al. submitted for publication). Radiolabeled test compounds were solvent-deposited onto ex vivo human skin mounted in Franz diffusion cells over a dose range exceeding 4.5 orders of magnitude, and permeation was measured over a 1-4 day period. At low doses, the permeation rate of NA was approximately 60-fold lower than that of its lower melting, more lipophilic analog, MN; at high doses an even greater difference was observed. The difference can be qualitatively explained based on higher lipid solubility and lower crystallinity of MN relative to NA. Dissolution-limited mass transfer through a lipid layer at the SC surface is suggested. Relevance of the results to practical skin care formulations was confirmed by a parallel study of NA in an o/w emulsion.