Development and Optimization of Thiolated Polymer-based Gastroretentive Drug Delivery Systems with Enhanced Mucoadhesion

Abstract

In this study, a novel class of mucoadhesive gastroretentive drug delivery systems (GRDDS) has been developed, focusing on the theory of mucoadhesion. The initial generation of mucoadhesive polymers demonstrated inefficient adhesion to gastrointestinal mucosa, thereby failing to ensure prolonged gastroretention. To address this limitation, thiolated polymers were employed, forming robust covalent bonds through thiol/disulfide exchange reactions with cysteine-rich subdomains of mucus. This innovative approach not only enhanced gastroretention but also facilitated biodegradation. The design of experiments (DOE) methodology was applied, specifically utilizing response surface methodology (RSM) and the Box-Behnken design. Thermo-gravimetric analysis (TGA) (X1) and NaCl-HCl concentration (X2) were selected as critical factors with varying levels (min, mean, max). The mucoadhesion potential, a key response variable, was systematically optimized through experimental runs to identify the ideal conditions. The selected optimal experimental conditions were then translated into the preparation of tablets, which were subsequently evaluated for gastroretention based on in vitro swelling and mucoadhesion studies. The results demonstrated that the developed GRDDS exhibited enhanced mucoadhesion potential, promising extended gastroretention capabilities. This research highlights the significance of thiolated polymers in designing efficient gastroretentive drug delivery systems and provides valuable insights into the optimization of mucoadhesion properties using a systematic experimental approach.