Controlled drug release properties of allopurinol-incorporated double-layered chitosan/starch patches for gout therapy.

To develop a sustained transdermal drug delivery system for gout treatment, double-layered patches containing allopurinol (ALP) were prepared using starch, chitosan, polyvinyl alcohol, and plasticizers. The chitosan-based first layer was designed to modulate the ALP release from the starch-based second layer, enabling sustained drug delivery for continuous therapeutic effect. The physicochemical properties of ALP and the prepared patches were characterized by physical properties, FE-SEM, FT-IR, 1H NMR and 13C NMR. The in vitro release profile was evaluated using artificial and porcine skin models. ALP was significantly released in a delayed manner over 48 h in artificial skin and 60 h in porcine skin, with release rates 2.32-4.16-fold and 1.91-5.77-fold slower, respectively, compared to single-layer patches. Mathematical modeling using the Higuchi, Fickian diffusion, and Korsmeyer-Peppas models indicated a pseudo-Fickian diffusion mechanism in buffer solution, whereas a non-Fickian diffusion mechanism predominated in both artificial and porcine skin. In addition, the transdermal penetration of ALP was visualized using riboflavin-loaded patches applied to porcine skin/agar block models. Xanthine oxidase inhibitory activity and colorimetric detection of ALP in the release solution confirmed the therapeutic potential of the double-layered patches for gout treatment. Cytotoxicity evaluation using HaCaT keratinocytes revealed excellent biocompatibility of the prepared double-layered patches.