Abstract

Effervescent matrix tablets offer a dynamic platform for controlling drug release by modulating water sorption, swelling, and matrix disintegration. This study presents a mechanistic and numerical framework to investigate the release kinetics of ibuprofen from hydroxypropyl methylcellulose (HPMC)-based matrices containing varying concentrations of effervescent agents. Under simulated gastric conditions (0.1 N HCl, pH 1.2), increased effervescence significantly enhanced water sorption and matrix porosity, accelerating drug release. To capture these effects quantitatively, a diffusion-based model was developed using Fick's second law in cylindrical coordinates, integrated with free volume theory to account for water-dependent diffusivity. A finite difference approach, coupled with Gauss–Newton optimization, was employed to estimate key diffusivity parameters with high precision. The model accurately reproduced experimental release profiles (R² > 0.99) and revealed how effervescence and HPMC content synergistically regulate swelling behavior and diffusivity. Estimated water diffusion coefficients ranged from 5.23 × 10⁻⁴ to 136.93 × 10⁻⁴ cm²/min across formulations, highlighting formulation-dependent mass transport dynamics. These findings highlight the value of integrated computational and experimental approaches for guiding the rational design of effervescent-based controlled release systems and advance our understanding of formulation-structure-function relationships in oral drug delivery.