DOI: https://doi.org/10.36347/sajp.2026.v15i07.001

Pages: 153-165

Oral drug delivery remains the most preferred route of administration because of its convenience, non-invasive nature, cost-effectiveness, and high patient compliance. However, the successful delivery of acid-labile drugs continues to present significant formulation challenges. Omeprazole, a proton pump inhibitor widely prescribed for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome, is highly unstable in acidic environments and undergoes rapid degradation in the stomach before reaching its primary absorption site in the small intestine. Consequently, specialized formulation approaches are required to protect the drug during gastric transit while ensuring efficient intestinal release. Among various oral delivery systems, pH-sensitive enteric-coated pellets have emerged as one of the most successful strategies for improving the stability and bioavailability of omeprazole. Multiparticulate pellet systems provide uniform distribution throughout the gastrointestinal tract, reduce variability in gastric emptying, and offer greater flexibility in controlling drug release compared with conventional single-unit dosage forms. The incorporation of pH-responsive polymers such as Eudragit® L100 and Eudragit® S100 enables site-specific release by exploiting physiological pH variations within the gastrointestinal tract. Recent developments in pelletization technology, enteric coating systems, and Quality by Design (QbD) methodologies have significantly improved the performance and reproducibility of omeprazole formulations. This review critically examines gastrointestinal physiology, pH-dependent drug delivery principles, the physicochemical characteristics of omeprazole, and the evolution of enteric-coated pellet systems. Particular emphasis is placed on sequential drug release strategies, polymer selection, formulation challenges, and emerging advances in pH-sensitive oral drug delivery. The review highlights the pote