Implementation of a Potential Industrial Green, Economical, and Safe Strategy to Enhance Commercial Viability of Liquid Self-Nanoemulsifying Drug Delivery System

<b>Background/Objectives</b>: Conventional solidification methods for liquid self-nanoemulsifying drug delivery systems face significant limitations. This includes complex manufacturing processes, high costs, and environmental concerns. This study aimed to develop and optimize a thermoresponsive self-nanoemulsifying drug delivery system (T-SNEDDS) for dapagliflozin as a sustainable alternative solidification technique. <b>Methods</b>: Oil and surfactant were selected based on solubility and emulsification studies. The Box-Behnken approach was used to examine the impacts of three independent variables (pluronic F127, propylene glycol, and dapagliflozin concentrations) on liquefying temperature and time. Optimized T-SNEDDS was characterized in terms of particle size, zeta potential, and dissolution performance. Stability assessment included centrifugation testing and a six-month storage evaluation. The green pharmaceutical performance was comparatively evaluated against five conventional solidification methods using ten adapted parameters. <b>Results</b>: Imwitor 308 and Cremophor EL were selected as optimal excipients for SNEDDS formulation. In addition, Pluronic F127 and propylene glycol were used to induce solidification during storage. The optimized formulation (8.60% <i>w</i>/<i>w</i> Pluronic F127, 10% <i>w</i>/<i>w</i> propylene glycol, and 5% <i>w</i>/<i>w</i> dapagliflozin) exhibited a liquefying temperature of 33.5 °C with a liquefying time of 100.3 s and a particle size of 96.64 nm. T-SNEDDS significantly enhanced dissolution efficiency of dapagliflozin (95.7%) compared to raw drug (42.4%) and marketed formulation (91.3%). Green pharmaceutical evaluation revealed that T-SNEDDS achieved the highest score compared to conventional approaches. <b>Conclusions</b>: T-SNEDDS represents a superior sustainable approach for SNEDDS solidification that offers enhancement in drug dissolution while addressing manufacturing, environmental, and economic challenges through its solvent-free and single-step preparation process with excellent scalability potential.