Topical delivery of lipophilic drugs from o/w Pickering emulsions

Abstract

Surfactant-free emulsions stabilized by solid particles (Pickering emulsions) have been evaluated in the terms of skin absorption of lipophilic drugs. The behavior of three formulations: a surfactant-based emulsion, a Pickering emulsion stabilized by silica particles and a solution in triglyceride oil, were compared in order to assess the effect of the surface coating of Pickering emulsions as new dosage forms for topical application. Such comparative investigation was performed in vitro on excised pig skin in Franz diffusion cells with all-trans retinol as model lipophilic drug. Surfactant-based (classical, CE) and Pickering (PE) oil-in-water emulsions containing retinol were prepared with the same chemical composition (except the stabilizing agent: surfactant or silica particles), the same droplet size and the same viscosity. No permeation through the skin sample was observed after 24 h exposure because of the high lipophilic character of retinol. Penetration of retinol was 5-fold larger for both CE and PE than for the solution in triglyceride. The distribution of retinol inside the skin layers depended significantly on the emulsions type: the classical emulsion allowed easy diffusion through the stratum corneum, so that large amounts reached the viable epidermis and dermis. Conversely, high storage of retinol inside the stratum corneum was favored by the Pickering emulsion. The retinol content in stratum corneum evaluated by skin stripping, demonstrated the increased retinol accumulation from PE. Therefore Pickering emulsions are new drug penetration vehicles with specific behavior; they are well-suited either for targeting the stratum corneum or aimed at slow release of drug from stratum corneum used as a reservoir to the deeper layers of skin.