ABSTRACT:
The present study focuses on the formulation and development of a thermosensitive in situ mucoadhesive nasal gel of Donepezil hydrochloride (DPH) aimed at improving its potential for brain-targeted delivery in the treatment of Alzheimer’s disease. DPH, a commonly used acetylcholinesterase inhibitor, faces challenges such as low brain availability and systemic side effects due to conventional oral administration. The intranasal gel system is designed to undergo sol-to-gel transition at physiological temperatures and adhere to the nasal mucosa, thereby enhancing residence time and providing a promising alternative route for efficient and patient-friendly delivery of DPH. To address these challenges, Poloxamer 407 was used for temperature-sensitive gelation, while Carbopol 934 imparted mucoadhesive properties. Various concentrations of both polymers were screened, and formulations were prepared and evaluated for gelation temperature, gelation time, mucoadhesive strength, viscosity, and pH. Batch F1, containing 17% w/v Poloxamer 407 and 0.2% w/v Carbopol 934, exhibited favorable gelation temperature (33±1.0°C), rapid gelation time (12±1.44 sec), developed viscosity, and strong mucoadhesion (4,232±180.40 dynes/cm²). In vitro diffusion study at 10hours 72±0.52% Drug release and ex vivo permeation confirmed enhanced drug release and mucosal permeability, especially with 1% Tween 80 as a permeation enhancer, achieving 71.24±0.43% drug permeation over 10hours. FTIR and DSC studies confirmed drug–polymer compatibility, and texture analysis supported its mechanical suitability. The Korsmeyer–Peppas model best described the release kinetics n = 1.298, indicating super case II transport. Short-term stability studies demonstrated that refrigerated storage preserved the formulation's physicochemical properties. The developed in-situ gel formulation (F1) shows promise as an effective non-invasive system for targeted nose-to-brain delivery of DPH.