Ex-vivo skin retention of crisaborole from microemulsion and micellar formulations

Abstract

The aim of the present work was to optimize the delivery of crisaborole to the skin, incorporating the drug in topical formulations with a texture suitable also for application to the hairy skin. In particular we focused on microemulsions and micelles. As reference, the concentration of crisaborole in skin layers obtained with the commercial ointment Eucrisa®, was considered. Two microemulsions, one w/o and one o/w, were tested ex-vivo and both produced drug deposition into the skin comparable to the commercial formulation, but with higher delivery efficiency and with a non measurable permeation across the skin. Solutol®, TPGS and Soluplus® at different concentration were used for the preparation of crisaborole micellar solutions. Compared to the commercial formulation, all the micellar systems produced lower drug concentration in the skin layers, with the only exception of Soluplus® 6 %. However, due to differences in drug loading and thus in the applied dose, the delivery efficiency of all the formulation tested was higher compared to the commercial ointment. Moreover with Soluplus® 6 % formulation, a 5-fold increase in the retained/permeated ratio compared to the ointment was obtained. Two-photon microscopy studies showed that Soluplus® 6 % micelles do not permeate intact across the skin but disassemble in correspondence of the tissue surface.