Design‐Expert Assisted Formulation Development, Optimization, and Evaluation of Selegiline and Biochanin A Loaded Self‐Nanoemulsifying Drug Delivery System

The goal of the work was to formulate, optimize, and evaluate liquid‐Self‐nanoemulsifying drug delivery system (L‐SNEDDS) co‐loaded with Selegiline (SEL), a monoamine oxidase type B (MAO‐B) inhibitor, and Biochanin A (BCA), a potent adjunctive neuroprotective agent found in Trifolium pratense , to enhance oral delivery and accelerate anti‐Parkinsonian efficacy for the management of Parkinson's disease (PD). Propylene glycol was chosen as co‐surfactant, Tween 80 as surfactant, and peppermint oil as oil phase after excipients screening, as this combination exhibited the broadest emulsification region in pseudo‐ternary phase diagram. A systematic Quality‐by‐Design (QbD) approach was adopted, and formulation variables were optimized using Design‐Expert software to obtain an optimized L‐SNEDDS formulation with desirable physicochemical attributes. Dilution of the optimized SNEDDS led to the spontaneous formation of a stable aqueous nanoemulsion exhibiting a droplet size of 110.9 nm, polydispersity index (PDI) 0.265, transmittance of 98.86 ± 0.37%, zeta potential of −16.3 mV, viscosity of 6.35 ± 2.51 cP, self‐emulsification time of 27.35 s, and conductivity of 196.23 ± 0.324 μS cm −1 . In vivo studies showed that SEL‐BCA‐loaded SNEDDS exhibited better oral bioavailability than pure SEL‐BCA suspension. Notably, SNEDDS achieved higher brain C max values for SEL (5.6 ± 0.41 μg mL −1 ) and BCA (13.84 ± 1.14 μg mL −1 ), as well as elevated plasma concentrations of SEL (6.51 ± 0.43 μg mL −1 ) and BCA (762.65 ± 16.82 μg mL −1 ). Collectively, the results underscore the potential of the SEL‐BCA SNEDDS as a combinational delivery platform that could improve the effectiveness of combination therapy for the management of PD.