SeDeM and Powder flow tools-assisted design of solid SMEDDS of luliconazole for antifungal therapy

BACKGROUND: Luliconazole is a broad-spectrum antifungal agent limited by poor solubility, skin permeation, and stability, which reduce its therapeutic efficacy in topical applications. AIM: This study aimed to develop a solid self-microemulsifying drug delivery system (S-SMEDDS) of luliconazole to enhance its solubility, transdermal delivery, and formulation stability. MATERIALS AND METHODS: A liquid SMEDDS was optimized using the SeDeM tool and converted to solid form via adsorption onto Neusilin® US2 and wheat straw. SeDeM combined with Powder Flow Tester (PFT) guided flow optimization, and formulations were evaluated for ex vivo drug release, transdermal permeation, and antifungal activity against Aspergillus niger and Candida albicans. RESULTS: The solid SMEDDS powders became free flowing, showing enhanced ex vivo drug release (39% wheat straw, 29.74% Neusilin® US2, n = 3) and improved transdermal permeation (47.89% and 45.27%, n = 3), with strong antifungal activity against Candida albicans (zones of inhibition: 22 ± 1 mm and 20 ± 1.2 mm) but limited effect on Aspergillus niger. CONCLUSION: The S-SMEDDS platform enhanced luliconazole solubility, transdermal delivery, and stability, offering a safe, effective, and scalable topical formulation for fungal infections and a practical route for industrial-scale production.