Development, In Vitro Characterization, and Statistical Optimization of Rizatriptan Benzoate Solid Lipid Nanoparticles Using Central Composite Design

Migraine is the second most prevalent neurological disorder, affecting nearly one billion individuals annually. Rizatriptan benzoate (RZB), a first-line triptan for acute migraine therapy, is conventionally administered orally; however, its clinical efficacy is limited by poor solubility, extensive first-pass metabolism, and a short half-life, resulting in low bioavailability (< 45%). To overcome these challenges, the present study aimed to develop, optimize, and evaluate Rizatriptan benzoate-loaded solid lipid nanoparticles (RZB-SLNPs) for intranasal delivery. SLNPs were prepared by solvent emulsification-evaporation followed by ultrasonication, employing glyceryl monostearate as the lipid matrix and Poloxamer 407 as the surfactant. A 3² factorial design and Central Composite Design (CCD) were applied to systematically investigate the influence of lipid and surfactant concentrations on particle size, entrapment efficiency, and drug release. Nine formulations were developed and optimized through statistical modeling, which confirmed high model adequacy and predictive reliability. The optimized RZB-SLNPs exhibited a spherical morphology, smooth surface, mean particle size of 143.0 nm, high encapsulation efficiency, and biphasic sustained drug release. FT-IR and DSC analyses confirmed drug–excipient compatibility and thermal stability, while stability studies indicated superior preservation under refrigerated conditions. In-vitro release studies demonstrated controlled and continuous drug release, supporting the potential of SLNPs for prolonged therapeutic effect. Importantly, the optimized nanocarrier significantly improved permeability and stability, suggesting enhanced bioavailability and rapid onset of action via the intranasal route. Collectively, these findings highlight RZB-SLNPs as a promising strategy for effective migraine management by overcoming solubility, permeability, and metabolic barriers associated with conventional formulations.