Design-Expert Assisted Formulation Development, Optimization, and Evaluation of Selegiline and Biochanin A Loaded...

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.