Box–Behnken Design

Dapsone is a synthetic sulfone with antimicrobial and anti-inflammatory activity, but conventional topical formulations may provide limited skin penetration and short local retention. This study aimed to develop, optimize, and characterize a dapsone-loaded solid lipid nanoparticle (DDP-SLN) polymeric hydrogel for controlled dermal delivery. DDP-SLNs were prepared by hot homogenization followed by probe ultrasonication using glyceryl monostearate (GMS), soya lecithin, and Tween 80. A three-factor, three-level Box–Behnken design using Design-Expert® Version 13 was employed to optimize the formulation based on particle size, entrapment efficiency, and 12-h cumulative drug release. The optimized DDP-SLN dispersion was incorporated into Carbopol 934 hydrogel and evaluated for physicochemical, rheological, drug-release, and stability characteristics. The optimized DDP-SLN showed a particle size of 140.38 nm, PDI of 0.287, zeta potential of −35.0 mV, and entrapment efficiency of 87.93%. The hydrogel exhibited homogeneous texture, pH of 6.23 ± 0.08, viscosity of 8486.67 ± 70.95 cP, and spreadability of 18.42 g·cm/s. Cumulative drug release reached 87.90% over 12 h and followed the Higuchi model (R² = 0.9910), while the Korsmeyer–Peppas exponent (n = 0.612) indicated anomalous transport. The formulation remained stable under the evaluated storage conditions, demonstrating its potential as a topical delivery system for dapsone. The system was designed to enhance drug localization while providing sustained release and hydrogel performance. These findings demonstrate the suitability of combining SLN technology with a hydrogel to improve topical dapsone delivery and maintain formulation quality.