Using laser microporation to improve transdermal delivery of diclofenac: Increasing bioavailability and the range of therapeutic applications

The objective of the study was to investigate the effect of laser microporation, using P.L.E.A.S.E.® technology, on diclofenac delivery kinetics. Skin transport of diclofenac was studied from aqueous solution, propylene glycol and marketed formulations across intact and laser-porated porcine and human skins; cumulative permeation and skin deposition were quantified by HPLC. After 24 h, cumulative diclofenac permeation across skins with 150, 300, 450 and 900 shallow pores (50–80 μm) was 3.7-, 7.5-, 9.2- and 13-fold superior to that across untreated skin. It was also found to be linearly dependent on laser fluence; Permeation (μg/cm2) = 11.35 * Fluence (J/cm2) + 352.3; r2 = 0.99. After 24 h, permeation was 539.6 ± 78.1, 934.5 ± 451.5, 1451.9 ± 151.3 and 1858.6 ± 308.5 μg/cm2, at 22.65, 45.3, 90.6 and 135.9 J/cm2, respectively. However, there was no statistically significant effect of laser fluence on skin deposition. Diclofenac delivery from marketed gel formulations was also significantly higher across laser-porated skins (e.g. for Solaraze™, cumulative permeation after 24 h across treated (900 pores/135.9 J/cm2) and untreated skin was 974.9 ± 368.8 and 8.2 ± 3.8 μg/cm2, respectively. Diclofenac delivery from Solaraze™ across laser-porated porcine and human skins was also shown to be statistically equivalent. The results demonstrated that laser microporation significantly increased diclofenac transport from both simple and semi-solid formulations through porcine and human skin and that pore depth and pore number could modulate delivery kinetics. A similar improvement in topical diclofenac delivery in vivo may increase the number of potential therapeutic applications.

Laser microporation significantly increases diclofenac transport across the skin and enables a GI-sparing mode of administration.Figure optionsDownload as PowerPoint slide