Design, development and optimization of itopride hydrochloride loaded floating pellets by spheronization after compression method: In vitro and in vivo evaluation

Abstract

Background Gastroesophageal reflux disease is the most common disorder with a considerably high global prevalence. It is known to manifest with wide range of symptoms. Prokinetic drugs are commonly recommended in treating gastric reflux in addition to antacids and antisecretory drugs. Itopride, a prokinetic agent, has found to improve symptoms of gastroesophageal reflux disease. It acts as D2 antagonist and acetylcholine esterase inhibitor. Objective This research aimed to develop a gastro retentive system using a dual approach of floating and mucoadhesion.The retention of the formulation was estimated by in vitro floating time and in vivo pharmacokinetic study. Methodology: Different batches of pellets were prepared using ethylcellulose, Eudragit S100 and Carbopol 934 with Itopride hydrochloride by compression and spheronization method. Central composite design (32) was applied to find the effect of independent variables (concentration of Eudragit S100 and ethylcellulose), on dependent variables (floating time and percent drug release). In vivo gastric retention and bioavailability were done on rabbits for optimized pellets formulation. Results All developed formulations passed general evaluations test for pellets (P1-P13). The optimized pellets resulted in the in vitro percent itopride hydrochloride release (97.84%) and (9.3hrs) floating time. In vivo residence was nearly 8hrs and bioavailability was 52.87 ± 0.15 µg/mL/h. Besides, pellets have showed the drug release by sustained action for 12hrs. Conclusion The experimental design of pellets formulation concluded that mucoadhesion with floating approach was suitable for gastric retention and sustained the release of the drug. So, this approach might be useful in controlling the reflux of stomachal fluid.