Rutin-loaded film-forming spray for accelerated wound repair: a QbD-guided translational approach

Wound healing remains a major clinical challenge, necessitating advanced topical systems that accelerate repair while minimizing complications. Rutin, a flavonoid with potent antioxidant, anti-inflammatory and angiogenic properties, suffers from poor solubility and instability, limiting therapeutic application. To overcome these drawbacks, a rutin-loaded film-forming spray (FFS) was developed using a Quality by Design (QbD) framework and optimized via a Box–Behnken design. Eudragit® RLPO and Eudragit® E100 were employed as film-forming polymers, propylene glycol as a plasticizer, and menthol as a permeation enhancer. The optimized formulation, CO-RUT (F1), exhibited favorable physicochemical characteristics, including rapid drying (56 ± 2 s), suitable viscosity (3.8 ± 0.076 cPs), and uniform drug content (95.3 ± 2%). In vitro release demonstrated sustained delivery over 8 h (86.7 ± 1.6%), following Korsmeyer–Peppas kinetics indicative of anomalous diffusion. Ex vivo permeation achieved 97.8% cumulative permeation, attributed to the synergistic effects of menthol and propylene glycol. Most critically, in vivo wound healing studies in rats showed complete wound closure by day 16, significantly outperforming marketed formulations and controls. Histopathological examination confirmed superior epithelialization, collagen deposition, and angiogenesis. This study establishes a stable, patient-compliant FFS that integrates QbD principles with robust experimental design, achieving enhanced topical delivery and therapeutic performance. The CO-RUT (F1) formulation demonstrates strong translational potential as a novel wound-healing platform and provides a methodological framework for developing next-generation film-forming sprays.