Pharmaco-Scintigraphic Evaluation of Skin Permeation and Retention of Nimesulide 1% Spray in Healthy Human Volunteers

Objective: This study aimed to evaluate the cutaneous absorption and retention of a novel topical nimesulide 1% spray formulation using gamma scintigraphy. Oral nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, though effective in acute pain, osteoarthritis, and dysmenorrhea, is associated with systemic adverse effects that restrict long-term use, underscoring the need for safer, localized alternatives. A topical spray formulation has the potential to address this gap by delivering the drug directly to the site of inflammation, ensuring rapid onset of action while minimising systemic exposure. Methods: In a single-application, open-label study, nimesulide 1% spray was radiolabeled with technetium-99m (⁹⁹ᵐTc) and applied to the dorsal skin of six healthy adult volunteers. Gamma scintigraphy, a validated non-invasive imaging technique, was employed to monitor penetration and retention in real time. Results: All six volunteers completed the study, and no adverse events were reported. Gamma scintigraphy demonstrated early localization of the radiolabeled formulation at the site of application, with the radiotracer remaining detectable throughout the 180 min observation period. ROI-based analysis demonstrated temporal variation in the skin-associated radiotracer signal, with an increasing trend during the early observation period and a separate quantitative profile showing the highest observed value at an intermediate time point followed by lower values at subsequent assessments. Among the evaluated radiolabeling conditions, the highest observed mean radiolabeling efficiencies were 97.73±4.92% at 30 °C and 95.94±4.78% at pH 7. No inferential statistical comparisons were performed between imaging time points or radiolabeling conditions. Conclusion: This exploratory pharmaco-scintigraphic study demonstrated the localization and temporal retention of radiolabeled nimesulide 1% spray at the application site following topical administration. These imaging findings provide preliminary information on the cutaneous distribution of the formulation and support further studies to evaluate its pharmacokinetic and clinical performance.