Formulation, Optimization & evaluation of sulfasalazine-loaded niosomal gel for treatment of rheumatoid arthritis

ABSTRACTBackground: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder affectingapproximately 0.5–1% of the global adult population, characterized by progressive joint damage and significantdisability. Sulfasalazine, a cornerstone conventional synthetic disease-modifying antirheumatic drug(csDMARD), demonstrates proven efficacy but is limited by poor oral bioavailability (<15%), gastrointestinalintolerance, hepatotoxicity, and unpredictable pharmacokinetics. Transdermal delivery via niosomalnanocarriers represents a promising strategy to overcome these limitations.Objective: This study aimed to formulate, optimize, and comprehensively evaluate sulfasalazine-loadedniosomal gel using a Quality by Design (QbD) approach for enhanced transdermal delivery in rheumatoidarthritis treatment.Methods: Sulfasalazine-loaded niosomes were prepared by thin-film hydration using Span 60 and cholesterol,optimized via Box-Behnken design (surfactant:cholesterol ratio, hydration temperature, sonication time).Critical quality attributes, including vesicle size, polydispersity index (PDI), entrapment efficiency (EE%), andzeta potential, were evaluated. The optimized niosomal dispersion was incorporated into Carbopol 934P gelmatrices and characterized for physicochemical properties, in vitro release, and stability.Results: The optimized formulation (F-Opt) exhibited vesicle size 187.4 ± 8.2 nm, PDI 0.218 ± 0.024, zetapotential −28.6 ± 2.4 mV, and entrapment efficiency 78.2 ± 3.6%. TEM and SEM confirmed spherical,unilamellar morphology. The niosomal gel (F-NG3, 1.5% Carbopol) demonstrated sustained release over 24hours (85.4% cumulative release) following Higuchi kinetics, significantly superior to plain drug gel (94.6%burst release). Stability studies under accelerated conditions (40°C/75% RH) confirmed 6-month stability withacceptable parameter variations.Conclusion: The developed sulfasalazine-loaded niosomal gel represents a promising transdermal platform forRA therapy, offering enhanced local drug delivery, sustained release, reduced systemic toxicity, and improvedpatient compliance compared to conventional oral administration.