Design and Optimization of Remdesivir-Loaded Eudragit L۱۰۰ Floating Microspheres: A ۳² Factorial Design Approach for Enhanced Pharmacokinetics and Gastro-Retentive COVID-۱۹ Therapy

The current research sought to establish and evaluate a gastro-retentive drug delivery system of Remdesivir-loaded floating microspheres utilizing a ۳² factorial design. Microspheres were formulated by the emulsion solvent diffusion method, employing Eudragit L ۱۰۰ as the primary polymer. Among the nine formulations developed, the optimized batch (OREL) exhibited favourable physicochemical characteristics, including a mean particle size of ۰.۲۵۴ µm, high entrapment efficiency (۷۶.۳۲%), and sustained drug discharge of ۸۱.۱۲% over ۱۲ hours. The microspheres demonstrated good stability with a polydispersity index of ۰.۲۴۵ and a zeta potential of -۲۳.۵ mV. Drug release kinetics followed both zero-order and Higuchi models, indicating a diffusion-controlled mechanism. FTIR and DSC analyses confirmed the absence of significant drug excipient interactions, ensuring chemical compatibility. In vivo radiographic studies using barium sulphate (BaSO₄) confirmed gastric retention for over ۱۰ hours. Pharmacokinetic studies showed enhanced oral bioavailability and a prolonged half-life of Remdesivir compared to the unmodified drug. This is the first report on the successful development of floating microspheres for Remdesivir, offering a sustained-release profile and improved therapeutic potential. The system effectively reduces dosing frequency and may enhance patient compliance in antiviral therapy.

کلیدواژه ها:

remdesivir ، Gastro-retentive drug delivery system ، Floating microspheres ، Controlled release ، Eudragit L۱۰۰