In Vitro Characterization of Multi-Source Omeprazole Capsule Dissolution Performance Under Biorelevant Conditions

Abstract

Regulatory requirements for drugs approval in several countries allow pharmaceutical companies to market drug products after providing evidence of compliance with pharmacopeial quality requirements and good manufacturing practices, a policy that reduces drug treatment cost and increases accessibility. On the other hand, these policies lead to pharmaceutical markets characterized by a large share of similar drug products that favor price-oriented competition, thereby discouraging pharmaceutical innovation and increasing productrelated variability in therapeutic response, potentially compromising patient outcomes and healthcare costs. Omeprazole, a widely prescribed drug for gastric secretion disorder treatment, has been historically marketed in Uruguay without the requirement of bioequivalence. The performance of omeprazole formulations, particularly the enteric-coated microgranules, have a significant impact on oral bioavailability because omeprazole is highly labile under acidic conditions. In this work, we aimed to assess the biopharmaceutical characteristics of 11 multi-source omeprazole (20-mg) capsules using in vitro biorelevant dissolution testing. The study included evaluations of enteric-coating performance, pH-dependent omeprazole degradation kinetics, and in vitro dissolution testing to simulate single and multiple doses. The findings revealed important variations in the enteric-coating performance among the tested formulations, with some products showing considerable drug release at pH levels under which the drug is rapidly degraded (pH ≤ 4.0). Dissolution testing revealed suboptimal results for several drug products and high formulation-related variability in omeprazole release profiles, which could potentially affect in vivo performance. This study highlights the need for biorelevant assessment of pharmaceutical quality for multi-source drug products.