Self-adhesive thin films for topical delivery of 5-aminolevulinic acid

Abstract

Self-adhesive thin-films have been developed as a topical delivery system for 5-aminolevulinic acid (ALA). The thin films are suitable for use during the photodynamic therapy of epithelial skin tumors. They are composed of a combination of the lipophilic polymer Eudragit NE and the lipophilic plasticiser acetyl tributyl citrate (ATBC). Because of its hydrophilicity, ALA forms suspension systems within these thin films, as evidenced by light microscopy. ALA release measured using Franz cells is very rapid from a Eudragit NE thin film loaded with 10% w/w ALA (200 μg ALA after 2.5 h), and even higher when ATBC is included. A Eudragit NE/ATBC (1: 2) thin film loaded with 20% w/w ALA releases 2000 μg ALA after 3.5 h. Combined release/permeation of ALA through excised membranes of human stratum corneum plus epidermis yielded fluxes of 50–100 μg ALA within 5 h for the Eudragit NE/ATBC (1: 2) thin film. The ATBC acts as a permeation enhancer for ALA. Scanning electron microscopy of the thin film surface shows protruding ALA particles which rapidly dissolve on contact with an aqueous medium. This surface dissolution mechanism is the cause of the rapid ALA release and hence also the high skin permeation in vitro. The mechanical properties of the thin films were also briefly examined. Adhesive strength increases with higher ATBC loading and decreases with higher ALA loading. Internal cohesion decreases with greater ATBC loading and increases with higher ALA loading. As part of this project, an improved derivatisation assay for gradient HPLC of ALA with 9Fluorenylmethyloxycarbonylchloride is also presented.