Arthritis is a persistent inflammatory disease that needs long term treatment, although traditional NSAIDs like flurbiprofen usually show side effects being systemic and low drug penetration at the inflamed location. As a way of overcoming these shortcomings, the current study was set out to design and optimize an ionically gelated flurbiprofen loaded nanogel. The nanoparticles were developed through different polymer concentration, cross-linker concentration, the speed of stirring, time of stirring, and time of sonication after which they were incorporated in a thermosensitive pluronic F127 gel. The optimized nanoparticles had a particle size of less than 200 nm, and a narrow PDI, positive zeta potential, and high entrapment. In vitro release experiments revealed a biphasic release which was characterized by an initial burst and sustained release over 24 hours. The end nanogel formulation was found to have appropriate pH, spreadability, and stability at refrigerated and accelerated conditions. In general, the flurbiprofen nanogel is optimized to be the most effective local drug delivery system in treating arthritis and it has good therapeutic efficacy, with little systemic adverse effects.