DEVELOPMENT AND FABRICATION OF TAPINAROF-LOADED MENTHOSOMAL GEL TO TREAT PLAQUE PSORIASIS

Objective: The study aimed to develop and optimize a Tapinarof-loaded menthosomal gel for improved topical delivery in the treatment of plaque psoriasis. The objective was to enhance solubility, drug retention, skin permeation, and formulation stability using a menthol-integrated vesicular system. Methods: Menthosomes were prepared using the thin-film hydration technique and optimized using a 2³ factorial design to evaluate the influence of phosphatidylinositol, cholesterol, and menthol on vesicle size, zeta potential, and entrapment efficiency. The optimized formulation was incorporated into a carbopol-based gel and evaluated for physicochemical properties, in vitro release, ex vivo permeation, and stability over 90 days. Results: The optimized formulation (PF6) containing 200 mg phosphatidylinositol, 10 mg cholesterol, and 100 mg menthol demonstrated a vesicle size of 267.9±11.7 nm, zeta potential of –32.6±1.6 mV, and entrapment efficiency of 92.7±1.8%. Upon gel incorporation (MG2), the formulation showed a pH of 6.75±0.12, viscosity of 15,680±512 centipoise (cP), and drug content of 97.9±1.5%. Ex vivo permeation showed 86.4±3.0% drug permeated in 12 h with a flux of 52.15±1.98 µg/cm²/h. The gel remained stable over 6 mo under both long-term (25 °C/60% RH) and accelerated (40 °C/75% RH) conditions with acceptable changes in performance parameters meeting ICH stability criteria. Conclusion: The menthosomal gel showed 3.2-fold higher skin permeation and 2.8-fold greater drug retention than plain gel, indicating superior dermal delivery. However, further studies on bioavailability, systemic exposure, and comparative efficacy are needed for clinical translation. In vivo evaluation is recommended for further validation.