Formulation development and evaluation of rotigotine mucoadhesive nanoemulsion for intranasal delivery

Rotigotine, a non-ergot dopamine agonist, is used in the management of early Parkinson's disease (PD) as monotherapy or an adjunct to levodopa. However, its clinical application is limited due to poor oral bioavailability (1%), high first-pass metabolism and fast plasma elimination (half-life of 5-7 h). The aim of this study was to develop and evaluate rotigotine mucoadhesive nanoemulsion (RMNE) for intranasal delivery. In this study, RMNE was developed and evaluated for physico-chemical characteristics, morphology, thermodynamic stability, in vitro release, mucoadhesive strength, and ex vivo permeation. Photon correlation spectroscopy and transmission electron microscopy analysis demonstrated that developed RMNE had a nanodroplet size of < 200 nm with nearly spherical size, while thermodynamic stability studies confirmed its stability. Addition of 1% chitosan in the nanoemulsion (NE) resulted in improved mucoadhesive property and permeation rate of the formulation across mucosa in comparison to NE without chitosan. In vitro release rate of rotigotine from RMNE was lower compared to the rotigotine NE (RNE), suggesting extended drug release due to the chitosan coating. The cumulative quantity of 85.23 +/- 0.39% rotigotine permeated through the nasal mucosa from RMNEF, whereas only 65.25 +/- 0.13% from RNE1 at 4 h. The overall enhancement ratio was found to be 1.40, which indicates better permeability of the mucoadhesive formulation compared to RNE. The development of RMNE may provide a promising approach for the effective delivery of rotigotine in the brain, improving the bioavailability of rotigotine for the better management of PD.