Development, Optimization, and Mechanistic Evaluation of Polymeric Matrix-Based Transdermal Patches of Posaconazole for Sustained Drug Delivery

Abstract

Posaconazole is a broad-spectrum antifungal agent with limited oral bioavailability due to poor aqueous solubility and variable gastrointestinal absorption, necessitating alternative delivery approaches. The present study aimed to develop and optimize a polymeric matrix-based transdermal drug delivery system to achieve sustained release and enhanced skin permeation. Transdermal patches were prepared using the solvent casting technique with hydroxypropyl methylcellulose and ethyl cellulose in varying ratios, along with polyvinylpyrrolidone, polyethylene glycol 400 as plasticizer, and propylene glycol as permeation enhancer. Preformulation studies confirmed favourable physicochemical properties, including suitable lipophilicity (log P ~3.18) and compatibility with excipients. The developed patches were evaluated for physicochemical characteristics, in vitro drug release, kinetic modelling, ex vivo permeation, surface morphology, and stability. Among all formulations, F7 exhibited optimal performance with high drug content (99.1%), excellent flexibility, and uniform thickness. It achieved 94.2% drug release over 24 hours with a biphasic profile. Release kinetics followed the Higuchi model with anomalous transport behaviour. Ex vivo studies demonstrated superior permeation with maximum flux and minimal lag time. Stability studies indicated minimal variation, confirming robustness of the formulation. The optimized system shows strong potential for controlled transdermal delivery.