DESIGN AND EVALUATION OF A SPANLASTIC-BASED TRANSDERMAL PATCH OF DONEPEZIL HYDROCHLORIDE MONOHYDRATE FOR ALZHEIMER'S DISEASE THERAPY

Abstract

Alzheimer's disease is a progressive neurodegenerative disorder that predominantly affects memory and cognitive function in older adults. Donepezil hydrochloride monohydrate, a reversible acetylcholinesterase inhibitor, is a first line therapy for Alzheimer's disease, but its oral administration is limited by extensive hepatic first-pass metabolism, variable bioavailability, and gastrointestinal side effects that compromise patient compliance. To address these limitations, the present study aimed to design and evaluate a spanlastic-based transdermal patch of donepezil hydrochloride monohydrate as an alternative delivery strategy. Spanlastic vesicles were prepared by the ethanol injection method using Span 60 as the vesicle-forming agent and Tween 80 as the edge activator, and the optimized dispersion was incorporated into a hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP K-30) polymeric matrix to fabricate transdermal patches by solvent evaporation. The formulation was characterized for drug excipient compatibility, particle size, zeta potential, entrapment efficiency, and in vitro cytotoxicity, and the resulting patches were evaluated for their physicomechanical properties. The optimized formulation produced nanosized vesicles with a mean particle size of 399 nm and a zeta potential of +1.8 mV, and entrapment efficiency reached 77 ± 5.29%, indicating satisfactory drug encapsulation. Fourier-transform infrared (FTIR) spectroscopy confirmed the absence of chemical interaction between donepezil hydrochloride and the formulation excipients. Cytotoxicity assessment on SK-N-SH human neuroblastoma cells by the MTT assay confirmed good biocompatibility across the tested concentration range, and the fabricated patches showed acceptable thickness, weight uniformity, folding endurance, surface pH, and drug content. Collectively, these findings suggest that spanlastic-based transdermal patches represent a promising, non-invasive alternative to oral donepezil therapy for the management of Alzheimer's disease and warrant further evaluation through ex vivo permeation and in vivo pharmacokinetic studies.