Optimization and evaluation of gastro-expandable film of Eudragit S100 and ethylcellulose by using the design of experiment

The aim of the present study was to develop and optimize a gastroretentive expandable film system of itopride hydrochloride using ethylcellulose and Eudragit S100 as film-forming polymers and triethyl citrate as a plasticizer, in order to enhance gastric retention and oral bioavailability. The gastroretentive expandable film was prepared by the solvent-casting method using a solvent system comprising ethanol and dichloromethane (1:1). A 2-factor, 3-level central composite design was employed to optimize the formulation variables. The prepared films were characterized using FTIR, DSC, XRD, and SEM to evaluate drug-excipient compatibility and solid-state properties. The films were assessed for folding endurance, floating time, in-vitro drug release, and gastroretention behavior. In-vivo pharmacokinetic studies were conducted in New Zealand white rabbits, and pharmacokinetic parameters (Cmax, Tmax, AUC, MRT, and t1/2) were determined from plasma concentration–time profiles. Stability studies were performed on the optimized formulation. The optimized expandable film demonstrated excellent mechanical strength with a folding endurance of 146 ± 2.1, rapid floating (9 ± 0.45 min), and nearly complete in-vitro drug release (98.9 ± 0.27%). The formulation exhibited gastroretention for more than 8 h. In-vivo pharmacokinetic evaluation revealed improved absorption, with a relative bioavailability of 106.14% compared to the marketed formulation (GANATON SR). The optimized film remained stable under storage conditions, as confirmed by stability studies. The developed gastroretentive expandable film system of itopride hydrochloride successfully achieved prolonged gastric retention, enhanced drug release, and improved oral bioavailability. This delivery system represents a promising and stable alternative to conventional sustained-release formulations for drugs requiring extended gastric residence.