Thermosensitive Mucoadhesive in-Situ Nasal Gels for Nose-to-Brain Delivery of Rivastigmine Hydrogen Tartrate: Formulation Strategies, Evaluation and Future Perspectives

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and cognitive decline. Although Rivastigmine Hydrogen Tartrate is widely used for symptomatic treatment, its clinical efficacy is limited by extensive first-pass metabolism, short half-life, gastrointestinal side effects, and poor penetration across the blood–brain barrier (BBB). Intranasal drug delivery has emerged as a promising alternative because it enables direct nose-to-brain transport through the olfactory and trigeminal pathways, bypassing the BBB. Thermosensitive mucoadhesive in-situ nasal gels remain in a liquid state during administration and rapidly transform into a gel at nasal physiological temperature, thereby prolonging nasal residence time and providing sustained drug release. This review summarizes recent advances in thermosensitive in-situ nasal gel formulations of Rivastigmine Hydrogen Tartrate, highlighting formulation strategies, polymer selection, preparation methods, physicochemical evaluation, drug release kinetics, and stability studies. Current challenges, recent research, and future prospects for clinical translation are also discussed. Overall, thermosensitive mucoadhesive in-situ nasal gels represent a promising approach for improving brain targeting and therapeutic efficacy of Rivastigmine Hydrogen Tartrate in the management of Alzheimer's disease.