Formulation and Characterization of Multiparticulate System for Proton Pump Inhibitor using Combination Therapy for Peptic Ulcer.

Abstract

Introduction: The purpose of this study was to develop sustained-release enteric-coated granules of Amla extract and Esomeprazole Magnesium for the treatment of peptic ulcer. It is well known that Amla possesses anti-ulcer activity due to the phenolic compound gallic acid, which inhibits a gastric H+/K+ ATPase pump. Therefore, enteric-coated Amla extract granules were combined with Esomeprazole Magnesium granules to enhance the synergistic effect, mitigate adverse effects associated with esomeprazole magnesium and improve overall anti-ulcer activity, while the enteric-coated multiparticulate system ensures prolonged drug release with a minimum dose.

Methods: A Soxhlet extraction method was employed to obtain the Amla phenolic extract, using a solvent mixture of ethanol and water in a 7:3 ratio. Wet granulation techniques were utilized to prepare granules, and hydroxypropyl methylcellulose phthalate served as the enteric coating agent. The in vitro drug release and drug entrapment were used to optimize the enteric-coated granules of Amla extract and Esomeprazole Magnesium. An in vivo study was conducted in Wistar albino rats (120-140 g) of both sexes to demonstrate the antiulcer activity of the developed formulation against an aspirin-induced ulcerated rat model.

Results: Both in vitro and in vivo studies were conducted. In the in vitro studies, drug release was assessed at pH 1.2 (simulated gastric fluid) and pH 6.8 (simulated intestinal fluid). The results demonstrated negligible drug release in the simulated gastric fluid due to the protective enteric coating, while efficient drug release occurred in the simulated intestinal fluid. In the in vivo studies, the combination therapy showed a significant therapeutic effect compared to other treatment groups in an animal model.

Discussion: Amla extract and Esomeprazole Magnesium were combined to prepare sustainedrelease enteric-coated granules for the treatment of peptic ulcers. The phenolic substance gallic acid inhibits the gastric H+/K+ ATPase pump, hence enhancing anti-ulcer efficacy. The combination demonstrated substantial therapeutic efficacy in both in vitro and in vivo investigations.

Conclusion: The amla extract and esomeprazole magnesium enteric-coated granules with sustained release and negligible drug release in acidic pH were achieved. In the in vivo studies, the combination therapy demonstrated a significant positive effect in treating peptic ulcers in a rat ulcer model, as shown by assessments of various parameters such as ulcer index, total gastric juice acidity, hematological analysis, and histopathological evaluations.