Abstract
Background: Pelubiprofen (PBF) is a cyclooxygenase-2 inhibitor currently marketed as an oral tablet in South Korea. Oral dosing is limited by gastrointestinal variability, first-pass metabolism, which can reduce therapeutic efficiency and increase adverse effects. Transdermal drug-in-adhesive patches provide a noninvasive alternative that bypasses these limitations and enables controlled delivery through the skin. Methods: The solubility of PBF in ethanol was evaluated, and its adhesive compatibility was tested using acrylic- and silicone-based systems. Different drug-loaded formulations were prepared, and their miscibility was assessed. Several permeation enhancers were screened. The physicochemical properties were analyzed. In vitro permeation was studied using rat skin in Franz cells. Accelerated stability was tested at 40 °C and 75% relative humidity for three months. Results: PBF reached near saturation at 120 mg/mL in ethanol. Among the adhesives, Duro-Tak(®) 8076 showed the best compatibility with ethanol and PBF. Drug loading above 15% led to crystallization; 15% was selected as the optimal loading. The addition of 2% oleic acid (OA) significantly increased the permeation flux to 11.31 ± 1.50 μg/cm(2)/h, showing a 3.6-fold enhancement over the control and enhanced deposition in the stratum corneum and dermis. Based on the physicochemical evaluation, PBF was present in an amorphous state within the adhesive matrix. Stability studies revealed no recrystallization, with the drug content maintained at 97-100%. Permeation remained unchanged during storage. Conclusions: The PD-OA2 patch achieved stable drug incorporation, enhanced skin permeation, and robust stability. These findings support the potential of PBF as a clinically relevant alternative to oral PBF formulations for treating localized inflammation and pain.