Box–Behnken design

The study aimed to formulate, optimize and characterize ornidazole NLCs using glyceryl monostearate (GMS), oleic acid and Tween 80 and to incorporate the optimized dispersion into a topical gel. NLCs were prepared by hot homogenization followed by ultrasonication. A three-factor, three-level Box–Behnken design comprising 17 runs was used to investigate GMS concentration, Tween 80 concentration and homogenization time. Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, drug content and in vitro drug release were evaluated. FTIR and SEM were used for physicochemical and morphological characterization. The NLC dispersion was incorporated into a Carbopol 934-based gel and evaluated for pH, spreadability, viscosity and stability. The optimized formulation (F13) had a particle size of 222.8 nm, PDI 0.289, zeta potential −26.7 mV, entrapment efficiency 83.6% and drug content 91.0%. The optimized formulation showed sustained drug release, with 82.3% cumulative drug release reported at 12 h in the response-optimization section. The optimized gel showed pH 5.73 ± 0.03, spreadability 6.28 ± 0.21 g·cm/s and viscosity 5080 ± 78 cP. FTIR analysis showed retention of characteristic ornidazole peaks without major drug–excipient interaction. The optimized formulation remained physically stable during the reported 60-day study. The study demonstrates the feasibility of developing an ornidazole-loaded NLC topical gel using a Box–Behnken design. The optimized formulation exhibited nanoscale particle size, acceptable PDI, measurable negative zeta potential, good entrapment and sustained drug release, supporting further investigation as a topical delivery system.