Formulation and Optimization of Chitosan-Based Flurbiprofen Nanoparticles for Ocular Delivery: A Design of Experiments Approach

<i>This study aimed to design and develop flurbiprofen-loaded chitosan nanoparticles for ophthalmic drug delivery, with the objectives of enhancing formulation stability, sustaining drug release, and improving patient comfort. This study introduces an optimized chitosan-based nanoparticle system for ocular delivery of flurbiprofen, achieving high encapsulation efficiency, physiological compatibility, and sustained release for 20 h. The findings demonstrate a practical, patient-friendly approach that enhances drug bioavailability and stability compared with conventional eye drops. Flurbiprofen-loaded nanoparticles were prepared using gelation and optimized through a Box-Behnken design. The influence of formulation variables (0.1%-0.3% w/v chitosan concentration, 0.2-0.6 mL/min dropping rate, and 500-900 rpm mixing speed) was assessed. The optimized nanoparticles were evaluated for particle size, polydispersity index (PDI), zeta potential, pH, osmolarity, and entrapment efficiency (%). The optimized formulation was achieved at 0.2% (w/v) chitosan concentration, a dropping rate of 0.4 mL/min, and a mixing speed of 700 rpm. The nanoparticles exhibited a particle size of 110.0 ± 2.20 nm, PDI of 0.347 ± 0.03, and zeta potential of + 15.4 ± 3.8 mV. The entrapment efficiency was 80.89%. The formulation was adjusted to physiological conditions (pH 6.7, osmolarity 300 mOsm/kg). <i>In vitro</i> studies showed a controlled release of flurbiprofen over 20 h. The optimized chitosan-based nanoparticle system demonstrated favorable physicochemical stability, high encapsulation efficiency, and sustained release of flurbiprofen. Compared with conventional ocular formulations, this structured nanoparticle delivery system offers superior drug retention and extended therapeutic action.</i>