Nose-to-brain delivery of rotigotine redispersible nanosuspension: In vitro and in vivo characterization

Abstract

Rotigotine (RTG) is an anti-Parkinson's drug approved by the USFDA to treat motor and non-motor symptoms of both early and advanced stages of the disease. However, issues like poor aqueous solubility, low oral bioavailability (<1%), first-pass metabolism, low systemic bioavailability (∼37%) and low brain bioavailability demean the therapy. This work developed poloxamer-stabilized RTG-Nanosuspension for intranasal (i.n.) administration. RTG-Nanosuspension was optimized using Box-Behnken design with critical variables affecting the responses, viz. particle size and PDI. The optimized RTG-Nanosuspension showed mean particle size of 73 nm and PDI of 0.286. Lyophilized RTG-Nanosuspension was also characterized for drug crystallinity, interactions, and morphology. The lyophilized RTG-Nanosuspension showed good stability and was a porous structure. The first 15 min of in vitro dissolution showed 95% cumulative drug dissolved from RTG-Nanosuspension formulation. RTG-Nanosuspension showed 20-fold increase in nasal permeation. The nasal ciliotoxicity study showed both RTG-Nanosuspension and drug dispersion were safe for i.n. delivery. An in vivo study showed that optimized RTG-Nanosuspension helped target RTG to the brain following i.n. administration. Overall, the RTG-Nanosuspension formulation showed potential in nose-to-brain delivery for targeted application in Parkinson's disease.