Design-Expert Assisted Optimization and Release Kinetic Modelling of Enalapril Nano-Sponges for Enhanced Oral Delivery

Abstract

The present investigation aimed to develop and optimize Enalapril-loaded polymeric nano-sponges to improve solubility, bioavailability, and sustained drug release using a statistically driven 2³ full factorial design. Nano-sponges were prepared by the solvent evaporation technique employing Eudragit S100, Eudragit L100, and ethyl cellulose as formulation variables. Design-Expert® software was utilized to evaluate the influence of formulation parameters on zeta potential and in vitro drug release. The optimized formulation demonstrated a particle size of 396.8 nm, polydispersity index of 0.174, zeta potential of -15.24 mV, and entrapment efficiency of 98.44%, indicating excellent colloidal stability and uniformity. In vitro dissolution studies exhibited sustained drug release over 12 h with enhanced dissolution behaviour compared to pure Enalapril. Drug release kinetics best fitted the Korsmeyer–Peppas model (R² = 0.9938), suggesting diffusion-controlled release. Comprehensive physicochemical characterization using FTIR, DSC, SEM, and particle size analysis confirmed compatibility between drug and polymers along with successful nano-sponge formation. ANOVA and response surface analysis established the statistical significance of formulation variables (p < 0.05). Stability studies performed under ICH accelerated conditions revealed minimal changes in drug content and release behaviour over 60 days. The study demonstrates the potential of nano-sponge-based systems as promising oral delivery platforms for poorly soluble antihypertensive drugs viz.enalapril and highlights the utility of factorial design in rational formulation optimization.