Background: One effective second-generation triptan for migraine attacks is sumatriptan. Following oral use, it has a 40% restricted bioavailability because of the first-pass metabolism. Aim: To develop the best intranasal Solusomes formula as a substitute that delivers into the brain directly, improving its bioavailability, and removing the first-pass outcome was the aim of this effort. Methodology: We developed solute formulations based on the Box-Behnken design and subsequently produced them via thin-film hydration. The quality by design technique was used to establish a correlation between the formulation parameters (Soluplus® and phosphatidylcholine (PC) concentrations) and signif¬icant quality powers (entrapment efficiency (EE%), vesicle size (VS), and polydispersity index (PDI)). Fourier trans¬form infrared spectroscopy (FTIR), optical microscopy, and an in vitro diffusion study were performed on the revised formula. Results: The enhanced formulation exhibited a VS of 93.76 nm, an EE% of 83.65%, and PDI 0.3362 with the least amount of error between the projected and observed values. Conclusion: This study offered a feasible and efficient intranasal formulation appropriate for further brain delivery research.
