DEVELOPMENT OF TRANSFERSOMAL BUCCAL PATCHES OF GALANTAMINE FOR ENHANCED BIOAVAILABILITY IN ALZHEIMER’S DISEASE THERAPY

Abstract

Background: Galantamine, an acetylcholinesterase inhibitor used in Alzheimer’s disease, exhibits low and variable bioavailability due to gastrointestinal metabolism and first-pass hepatic elimination. Buccal drug delivery offers a non-invasive route that bypasses first-pass metabolism and maintains systemic exposure. This work aimed to develop and evaluate transfersomal buccal patches of galantamine to enhance permeation and control release. Methodology: Galantamine-loaded transfersomes were prepared by thin-film hydration using phosphatidylcholine and edge activators, then incorporated into a mucoadhesive polymer matrix (PVA/HPMC/Carbopol/Eudragit L-100) via solvent casting. Formulations were characterized for vesicle size, zeta potential, deformability, entrapment efficiency, physicochemical properties, swelling, mucoadhesion, in vitro release, ex vivo buccal permeation, and stability. Result and Discussion: Transfersomes exhibited a mean size of 126.4 ± 4.8 nm, PDI ≈ 0.21, zeta potential −32.6 ± 1.4 mV, and entrapment efficiency 86.7 ± 2.5%. Optimized patches showed uniform thickness, high folding endurance (>300), drug-content uniformity (≈95–98%), and strong mucoadhesive strength, with PEG-plasticized films demonstrating superior swelling and residence time. Drug release followed diffusion-controlled (Higuchi-type) kinetics with near-zero-order behavior. Ex vivo permeation revealed a 2.5-fold increase in steady-state flux (3.21 ± 0.18 µg/cm²/h) and a higher permeability coefficient compared with the conventional oral formulation. Accelerated and saliva stability studies indicated no significant physicochemical changes. Conclusion: The integration of deformable transfersomes within a mucoadhesive buccal matrix enabled sustained diffusion-controlled delivery, significantly enhancing mucosal permeation. The transfersomal buccal patch represents a promising alternative to oral galantamine therapy, warranting in vivo pharmacokinetic and clinical evaluation.