<![CDATA[Background: Soursop leaves (Annona muricata L.) contain bioactive compounds including acetogenins, flavonoids, alkaloids, and tannins, which possess antioxidant, anti-inflammatory, and antitumor activities. Transdermal patch delivery systems offer significant advantages by bypassing hepatic first-pass metabolism, enabling controlled drug release, and improving patient adherence. Two independent formulation strategies were pursued: (1) a hydrophilic–hydrophobic PVP–Ethyl Cellulose (EC) matrix system, and (2) a chitosan-based biopolymer matrix system. Objectives: This study aimed to formulate and comparatively evaluate transdermal patches of soursop leaf ethanol extract using PVP K-30/ethyl cellulose (Study 1) and chitosan (Study 2) as polymer systems, and to determine the optimal formulation for each system based on physicochemical characteristics and in vitro diffusion performance. Methods: Ethanol extracts were prepared by maceration with 96% ethanol. Study 1 evaluated three PVP:EC ratios (F1: 1:1, F2: 1:2, F3: 1:3). Study 2 evaluated three chitosan concentrations (F1: 250 mg/50%, F2: 225 mg/45%, F3: 200 mg/40%). Both systems incorporated PEG 400 as plasticizer and oleic acid as penetration enhancer. Patches were evaluated for organoleptic properties, thickness, pH, folding endurance, and in vitro diffusion using Franz diffusion cells with phosphate buffer pH 7.4, measured by UV-Vis spectrophotometry at 266 nm. Results: Both polymer systems produced patches meeting pharmacopoeial physical requirements. Study 1: pH 5.26–5.47, thickness 0.1 mm, folding endurance >300; optimal formula F3 (PVP:EC = 1:3) achieved the highest cumulative diffusion of 119.087 µg/cm² at 360 min (R² calibration = 0.99909). Study 2: pH 4.30–4.59, thickness 0.35 mm, folding endurance >300; optimal formula F3 (chitosan 40%) achieved the highest cumulative diffusion of 327.44 µg/cm at 360 min with cumulative release of 0.655%. A clear inverse relationship between chitosan concentration and diffusion rate was established. Conclusion: Soursop leaf ethanol extract can be successfully formulated into transdermal patches using both PVP–EC and chitosan polymer systems. The chitosan-based system (F3: 40%) demonstrated superior total drug diffusion, while the PVP–EC system (F3: 1:3) produced a thinner, more uniform patch with controlled diffusion. Both formulations are promising candidates for further in vivo and stability studies.]]>
