Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline, amyloid-plaque deposition, tau hyperphosphorylation, and neuronal loss. It primarily affects the elderly and represents a growing global health burden. Current treatments, including cholinesterase inhibitors and NMDA receptor antagonists, provide only symptomatic relief and do not halt disease progression. Furthermore, frequent oral dosing often leads to poor patient adherence and fluctuating plasma drug levels, limiting therapeutic effectiveness. To address these challenges, advanced drug delivery systems have been explored to improve treatment consistency and patient compliance. Among them, long-acting injectable (LAI) formulations, particularly in situ forming implants (ISFIs), have gained considerable attention. ISFIs are typically composed of biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) dissolved in biocompatible solvents. Upon administration, these systems undergo phase inversion triggered by solvent exchange with physiological fluids, resulting in the formation of a solid depot at the injection site. This depot enables sustained and controlled drug release over extended periods, reducing dosing frequency and improving therapeutic stability. Despite these advantages, burst release during the initial phase inversion remains a critical limitation, potentially leading to transient drug overexposure and reduced long-term efficacy. This review discusses the pathophysiology of AD, the rationale for long-acting delivery approaches, and recent advances in ISFI technology, with emphasis on formulation strategies to control burst release and enhance therapeutic outcomes in Alzheimer's disease management.

Dighe Anjali, Deshmukh Rutik, Girdhar Devesh, Kalamkar Rajan

Neurodegenerative disorder; Long-acting injectables (LAIs); Burst release; Controlled release systems.