Preparation and characterization of Eudragit L 100-55/chitosan enteric nanoparticles containing omeprazole using general factorial design: in vitro/in vivo study

BACKGROUND AND PURPOSE: Omeprazole (OMP) is broadly used for the treatment of gastroesophageal reflux and other acid-related diseases. The current study aimed to prepare enteric-coated nanoparticles containing OMP to achieve a stable powder formulation easily prescribed in children. EXPERIMENTAL APPROACH: The nanoparticles were formed by complex coacervation method using chitosan (CTS) and Eudragit L100/55 (EU) and the impact of various formulation variables (the concentrations of EU solution and its volume ratio to CTS solution) were assessed using 3(2) fractional design. The mean particle size (PS), zeta potential (ZP), encapsulation efficiency (EE), and drug loading (DL) were determined. Finally, the pharmacological effects of the optimized OMP enteric nanoparticles were evaluated by an in vivo antiulcer study using Sprague-Dawley rats. FINDINGS/RESULTS: The highest desirability value was for formulation F5 (containing EU concentration 4 mg/mL and EU/CTS volume ratio 2:1). PS, ZP, EE, and DL of the optimized OMP-loaded nanoparticles were confirmed 810 ± 14 nm, -38.2 ± 1.8 mV, 83.1± 4.2%, and 13.1± 1.5%, respectively. in vitro release studies showed the pH sensitivity of nanoparticles and OMP release was pH-dependent. in vivo pharmacological assessment revealed that the optimized formulation was able to protect rat stomach against ulcer formation induced by indomethacin compared to the group that received normal saline which demonstrated severe peptic ulcer and hemorrhagic spots. CONCLUSION AND IMPLICATION: Our results indicated that the enteric EU/CTS nanoparticles were successfully prepared via a complex coacervation method and their efficacy could be comparable with commercial OMP pellets.