Quality by design approach for optimization, in-vitro and in-vivo evaluation of compression-spheronized itopride hydrochloride loaded gastroretentive pellets for the treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is the most common disorder with a significantly high global prevalence. Prokinetic drugs are commonly recommended for the treatment of gastric reflux, in addition to antacids and antisecretory agents. Itopride hydrochloride, a prokinetic agent, acts as a D2 receptor antagonist and an acetylcholinesterase inhibitor, improving GERD symptoms. The objective of this study was to develop a floating-type gastroretentive drug delivery system, which was further evaluated by in vitro and in vivo studies. Itopride hydrochloride-loaded gastroretentive pellets were prepared using pelletization followed by spheronization. The preparation of itopride-loaded gastroretentive pellets was optimized using a central composite experimental design (32), varying the concentrations of ethylcellulose and Eudragit S100 as independent variables, while floating time and percentage of drug release were considered dependent variables.The optimized batch was characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). It was then evaluated for mucoadhesion, in vivo gastric retention, and bioavailability in rabbits. The in vitro drug release from the optimized pellet formulation exhibited approximately 97.84% release over 10 h and maintained buoyancy for up to 9 h. In vivo gastric residence time was observed to be 6 h, with a bioavailability of 52.87 ± 0.15 µg/mL/h. Based on in vitro and in vivo findings, the developed gastroretentive mucoadhesive pellet formulation presents a promising drug delivery system for the treatment of GERD, potentially enhancing drug efficacy through prolonged gastric retention.