Eco – Pharmaceutical Design of a Helianthus Annuus Nanoemulcream: A QbD Optimization Strategy

Purpose This study aimed to develop an eco-pharmaceutical Helianthus Annuus (sunflower) oil nanoemulcream using a Quality-by-Design approach integrated with a Central Composite Design to optimize formulation and process variables for improved stability, skin compatibility, and therapeutic performance. Method Sunflower oil was characterized using GC–MS and ATR–FTIR analyses. Nanoemulsions were prepared by high-speed homogenization, and key factors surfactant concentration, homogenization speed, and time were optimized using CCD to minimize particle size. The optimized nanoemulcream was evaluated for physicochemical properties, droplet size, PDI, zeta potential, morphology (SEM), stability, skin irritation, antibacterial activity, in-vitro drug release, and release kinetics. Results The developed nanoemulsion exhibited a mean droplet size of 134.7 ± 34.1 nm, Z-average 166.9 nm, PDI 0.409, and zeta potential − 30.1 ± 2.3 mV, confirming uniform dispersion and electrostatic stability. The nanoemulcream showed suitable pH (6.2 ± 0.1), viscosity (28,500 ± 120 cP), spreadability (12.5 ± 0.5 g·s⁻¹), high drug content (94.2 ± 1.8%), and maintained stability over three months. In-vitro release studies (360 min) demonstrated superior drug release from the nanoemulsion (88%), followed by the nanoemulcream (64.8%), cream with sunflower oil (49%), and plain sunflower oil (30%). Kinetic modeling indicated diffusion-controlled and anomalous transport mechanisms, supported by Korsmeyer–Peppas n values between 0.45–0.89. The formulation was non-irritant in skin studies and showed moderate broad-spectrum antibacterial activity (MIC 110–140 µg/mL). Conclusion The QbD-guided development enabled a stable, skin-compatible, and therapeutically effective sunflower oil nanoemulcream. Enhanced release and controlled kinetics highlight its potential as a sustainable topical delivery system for natural bioactives.