Enhancing Nose- To- Brain Delivery of Piribedil: Development of a Nanosuspension Dispersed in Nasal in-Situ Gelling System

Abstract

Objective: This study focuses on improving the delivery of Piribedil, a poorly soluble drug, to the brain through the nasal route using a nanosuspension in a nasal in-situ gel. Methods: The nanosuspension was prepared using the sonoprecipitation method. Quality-by-Design (QbD) principles were used to optimize both the formulation and process parameters. The optimal process parameters were determined as sonication time (7.09 min), sonication amplitude (83.44%), and infusion rate (2.41 mL/min) with a desirability value of 0.970. Results: The nanosuspension exhibited an average particle size ranging from 46.7 nm to 50.1 nm, and polydispersity index values between 0.393 and 0.425. Zeta potential values ranged from -33.78 ± 1.86 mV to -35.06 ± 2.12 mV, indicating favorable stability. FTIR studies revealed molecular interactions between Piribedil and stabilizers. XRPD and DSC analyses showed the transition from a crystalline to an amorphous state in the nanosuspension. Dissolution studies demonstrated significantly accelerated dissolution for the Piribedil nanosuspension, attributed to its nanosize and improved wettability. Stability assessments confirmed the robustness of the nanosuspension. Conclusion: This innovative approach offers potential solutions for drug solubility challenges and blood-brain barrier penetration, holding promise for effective brain-targeted treatments.