Strategic Formulation and Optimization of a Febuxostat Nanoparticles Infused Topical Gel Using Quality‐by‐Design Principles for Enhanced Therapeutic Efficacy in Gout Management

Abstract Gout is a painful form of inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. This study aimed to develop a topical nanogel containing polymeric nanoparticles to enhance site‐specific delivery of Febuxostat (FXT) using a quality‐by‐design (QbD) approach. Febuxostat (FXT) nanoparticles were prepared by the solvent‐evaporation method; critical factors were screened with a Plackett–Burman design and optimized via a Box–Behnken design. The optimized nanoparticles (OBFN2) displayed a particle size of 228.2 ± 10 nm, PDI 0.161 ± 0.05, zeta potential + 33.1 mV, and encapsulation efficiency 50.6% ± 5%. Incorporation of OBFN2 into a Carbopol 934 gel yielded a nanogel that released 100% of FXT within 6 h, whereas the control gel containing micronized Febuxostat (FXT) required markedly longer. The topical nanogel therefore provides faster and more complete drug release at the target site, indicating strong potential to improve therapeutic efficacy and patient adherence in gout management.