QUALITY BY DESIGN ASSISTED FORMULATION, DEVELOPMENT AND OPTIMIZATION OF NANO SPONGES CONTAINING THIOCOLCHICOSIDE BY DESIGN OF EXPERIMENT (DOE) APPROACH

ABSTRACT Background: Thiocolchicoside has poor aqueous solubility, which may limit its effective delivery. Nanosponges provide a promising approach for improving drug encapsulation and achieving sustained drug release. QbD and DOE offer a systematic method for formulation optimization. Objective: To formulate and optimize Thiocolchicoside-loaded nanosponges using a QbD-based DOE approach to achieve high entrapment efficiency, suitable particle size, stability, and sustained drug release. Methods: Preformulation studies included solubility, pH, melting point, UV spectroscopy, and FTIR analysis. Thiocolchicoside showed poor aqueous solubility, a λmax of 366 nm, and linearity in the range of 5–30 µg/ml (R² = 0.9992). Nanosponges were prepared using β-cyclodextrin and diphenyl carbonate and optimized using a Box–Behnken design and Response Surface Methodology. The effects of formulation variables on particle size and entrapment efficiency were evaluated. Results: The optimized formulation showed a particle size of 309.8 nm, zeta potential of −28.6 mV, and entrapment efficiency of 95.89%. SEM confirmed the porous nanosponge structure. In vitro studies demonstrated sustained drug release for 12 h, following predominantly Zero-order kinetics with diffusion-controlled release. The formulation remained stable under both accelerated and room-temperature conditions. Conclusion: QbD-assisted optimization successfully produced Thiocolchicoside-loaded nanosponges with high entrapment efficiency, nanoscale particle size, good stability, and sustained drug release, demonstrating their potential as an effective controlled-release drug-delivery system. Keywords: Thiocolchicoside; Nanosponges; QbD; DOE; Box–Behnken Design; Response Surface Methodology; Entrapment Efficiency; Sustained Release; β-Cyclodextrin.