The present study aimed to develop and optimize a semaglutide-loaded nanoemulsion for enhanced oral delivery and improved formulation performance. Semaglutide-loaded nanoemulsions were prepared by the spontaneous emulsification method using Capryol® 90 as the oil phase, Tween® 80 as the surfactant, and Transcutol® P as the co-surfactant. A Box–Behnken Design (BBD) was employed to optimize formulation variables and evaluate their influence on particle size, entrapment efficiency, and cumulative drug release. Preformulation studies confirmed the suitability of the selected excipients and demonstrated adequate stability of semaglutide under formulation conditions. Fifteen experimental formulations were developed and characterized. The prepared nanoemulsions exhibited particle sizes ranging from 124.7 to 202.3 nm, entrapment efficiencies between 81.42% and 94.28%, and cumulative drug release values ranging from 67.1% to 87.5% after 8 h. ANOVA analysis revealed that oil concentration and surfactant concentration significantly affected the critical quality attributes of the nanoemulsion system. The optimized formulation (F16) showed a desirability value of 0.934 and exhibited an entrapment efficiency of 93.82 ± 0.4%, particle size of 126.10 ± 1.1 nm, and cumulative drug release of 86.94 ± 0.6%. Comparison with a marketed oral semaglutide formulation demonstrated improved release characteristics and superior nanoscale dispersion. The findings suggest that the developed semaglutide-loaded nanoemulsion represents a promising oral delivery system capable of enhancing drug solubilization, release behavior, and overall formulation performance.
Dhanush Ram Turkane*1 (Wed,) studied this question.