Solid lipid nanoparticles, or SLNs, have gained popularity recently as a possible drug delivery method. However, the idea of using SLNs for organ and site-specific drug administration is still in its early stages due to the difficulties associated with this approach. The aim of this study is to develop SLNs with improved pharmaceutical characterization and anti-arthritic efficacy. Tofacitinib citrate (TC)-loaded SLNs were created using the microemulsification method, with the addition of stearic acid, chitosan, and Tween 80 to improve skin permeability. Seventeen SLNs were developed and characterized for particle size, entrapment efficiency (EE), and percentage drug release according to the Box-Behnken design. The DSC analysis revealed a strong endothermic peak at 166.18°C, significantly different from the pure TC reported at 218.05°C. This indicates a notable alteration in the endothermic peak of the SLNs, demonstrating a relationship with the excipients used in this investigation. XRD study highlighted significant characteristic drug peaks at positions 21.06 and 23.63 (2ɵ). These peaks represented the modifications that were seen in pure TC. The SEM analysis of the optimized lipid nanoparticles showed a smooth surface and a spherical appearance. The particle size analysis of the optimized formulation showed an average size of 181.5 nm. Also, the polydispersity index (PI) revealed a value of 0.495, indicating homogeneous dispersion. The zeta value was 8.2 mV, indicating stability.