Zinc-Modified Mordenite Zeolite as a Molecular Carrier for Donepezil: A Framework for Drug Delivery Applications

TL;DR

This paper explores using zinc-modified mordenite zeolite to deliver donepezil, a drug for Alzheimer's, with high efficiency and controlled release.

Contribution

The study introduces zinc-modified mordenite as a novel, efficient, and stable drug delivery matrix for donepezil.

Findings

Zinc modification increased the surface area of mordenite from 62.1 to 85.4 m²/g and improved adsorption properties.

Donepezil was loaded with high efficiency (94-95%) and released 80-82% after 24 hours under simulated gastrointestinal conditions.

DFT calculations confirmed favorable adsorption energy and interactions without damaging the zeolite framework.

Abstract

The development of advanced drug delivery systems is essential for improving therapeutic efficacy, particularly in the treatment of neurodegenerative disorders such as Alzheimer’s disease. This study investigates zinc-modified mordenite zeolite (MR-ZN) as a novel platform for the controlled delivery of donepezil (DPZ), a cholinesterase inhibitor. Natural mordenite was modified with zinc, enhancing its surface area from 62.1 to 85.4 m2/g and improving its adsorption properties. Donepezil was successfully loaded at two doses (10 mg and 23 mg), achieving high loading efficiencies of 95% and 94%, respectively. Adsorption kinetics followed a pseudo-second-order model (R2 > 0.99), indicating that chemisorption predominates through coordination between DPZ functional groups and Zn2+ sites, while complementary physisorption via hydrogen bonding and van der Waals interactions also contributes to molecular stabilization within the zeolite framework. In vitro release studies under simulated gastrointestinal conditions demonstrated sustained and pH-responsive release profile with 80% and 82% of donepezil released after 24 h for 10 mg and 23 mg formulations, respectively. Density Functional Theory (DFT) calculations revealed favorable adsorption energy (−26.4 kJ/mol), while Bader and Electron Localization Function (ELF) analyses confirmed hydrogen bonding and electrostatic interactions without compromising the zeolite framework. These findings validate MR-ZN as structurally stable, efficient, cost-effective and biocompatible matrix for oral drug delivery. The combination of experimental data and theoretical modeling supports its potential to improve bioavailability and therapeutic performance in neurodegenerative treatment.

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