Transdermal delivery of the free base of 3-Fluoroamphetamine

Abstract

This work aimed to continue our effort in establishing the feasibility of 3-fluoroamphetamine (also known as PAL-353) to be a transdermal drug candidate by studying the delivery of the base form through the human cadaver skin in lieu of the previously investigated salt form, and for the first time using an EPIDERM™-reconstructed human epidermal model to predict the skin irritation potential of PAL-353, in support of development for a matrix-type transdermal delivery system. Passive and enhanced (with chemical permeation enhancers) transdermal delivery were investigated via in vitro permeation studies that were performed on Franz diffusion cells with dermatomed human cadaver skin. After 24 h, PAL-353 free base revealed high passive permeation of 417.49 ± 30.12, 1577.68 ± 165.41, and 4295.16 ± 264.36 μg/cm2, with applied formulation concentrations of 5.5 (F1), 20 (F2), and 40 (F3) mg/mL, respectively. Oleyl alcohol produced an approximately threefold steady-state flux enhancement at 5% or 10% w/w but may not be needed as the free base alone provided therapeutically relevant permeation. Further, it was predicted that therapeutically relevant delivery would be unlikely to cause skin irritation using the EPIDERM™-reconstructed human epidermal model. In conclusion, the present study further supported the development of PAL-353 transdermal delivery systems.