Optimized SNEDDS of Riluzole for Alzheimer’s Disease: Enhancing Solubility, Bioavailability, and Therapeutic Efficacy in Scopolamine-induced Rats Model

The hallmarks of Alzheimer’s disease (AD) include a gradual deterioration in cognitive abilities, hyperphosphorylation of tau proteins, and the aggregation of amyloid-beta (Aβ). Riluzole, a neuroprotective agent, shows promise in mitigating glutamate-induced excitotoxicity; however, its poor solubility (BCS Class II) limits its therapeutic efficacy. This study aimed to develop and optimize a self-nanoemulsifying drug delivery system (SNEDDS) to enhance Riluzole’s solubility, bioavailability, and therapeutic effects in AD. The formulation was optimized using Design Expert (BBD), with independent variables including oil (2–5%), surfactant mixture (Smix, 5–20%), and sonication time (30–60 s). The optimized SNEDDS were subjected to physicochemical characterization, a drug release study, gut permeation, and in vivo pharmacokinetic and behavioral assessments in scopolamine-induced AD rats. The optimized Riluzole SNEDDS showed a particle size of 136.5 nm, a polydispersity index of 0.264, zeta potential of − 26.13 mV, and transmittance of 91.3%, indicating nanoscale dispersion. In vitro drug release was significantly higher (84.65% in 12 h) than Riluzole suspension (34.94%). Gut permeation studies revealed 2.08-fold higher drug permeability with SNEDDS. Pharmacokinetic analysis showed 2.21-fold increased bioavailability (AUC₀₋ₜ 6437.92 ± 34.76 ng·h/ml) and 1.7-fold increased half-life compared to suspension. Behavioral assessments demonstrated significant memory improvement (p < 0.0001) in AD rats treated with Riluzole SNEDDS. The optimized Riluzole SNEDDS formulation significantly improved drug solubility, bioavailability, and cognitive function in AD rats, demonstrating its potential as an effective therapeutic strategy for AD.