Intranasal polymer/surfactant/HPβCD liquid and powder formulations of ropinirole in C57BL/6J mice markedly increased systemic and brain exposure versus oral or intranasal solution, with the powder showing the highest relative serum (≈1497%) and brain (≈541%) bioavailability.

By demonstrating substantially improved CNS delivery of an approved PD dopamine agonist, the work supports a translational route-optimization strategy to enhance symptomatic control and bypass first-pass/GI issues, though it lacks efficacy, safety, and disease‑modifying data.

Nasal administration has emerged as an effective alternative for drug delivery to central nervous system (CNS), particularly in neurodegenerative diseases. Ropinirole hydrochloride (RH) is used as a monotherapy or as an adjunctive combination with levodopa for the management of Parkinson's disease. However, RH undergoes extensive first-pass metabolism, thereby limiting the amount of drug reaching the CNS. The purpose of the present study was the determination of the pharmacokinetic parameters of RH when administered intranasally as colloidal dispersion [(P407/Tw80/HPβCD)/RH 10:5] and as a powder [(P407/Tw80/HPβCD)/RH 10:5 blended with mannitol/lecithin microparticles (25:75)] for brain targeting. In particular, the pharmacokinetic study was carried out in comparison with oral (per os) and IN administration of pure RH solution in C57BL/6J mice. The brain and serum distribution pharmacokinetics of the drug were studied applying the sparse sampling non-compartmental analysis (NCA). The pharmacokinetic profiles after intranasal and per os administration revealed the efficiency of intranasal administration in rapidly and effectively delivering RH, both to the CNS and bloodstream. The pre-eminence of the nasal formulations is witnessed by higher serum AUC and Cmax values after intranasal administration of formulations compared to the per os administration of RH solution. Notably, the intranasal administration of the RH powder resulted in the highest systemic bioavailability (Frel(Serum) = 1497 %) and brain exposure (Frel(Brain) = 541 %), suggesting a promising role for nasal delivery in targeting the CNS.