DEVELOPMENT AND BIOEQUIVALENCE STUDY OF ESOMEPRAZOLE BIPHASIC MICRO PELLETS TABLETS

Abm Mahfuz Ul Alam* and K. Hasan

ABSTRACT

The development of Esomeprazole Biphasic Micro Pellets Tablets, 20 mg & 40 mg, followed a structured approach based on the US FDA Guidance "Quality by Design for ANDAs: An Example for Immediate-Release Dosage Forms." This encompassed defining the Pharmaceutical Product Target Profile (PPTP), identifying Critical Quality Attributes (CQAs), conducting formulation development, optimizing formulation and process, and establishing a control strategy for commercial manufacturing. The formulation included enteric-coated micro pellets with different pH-dependent dissolution profiles, designed to deliver Esomeprazole in two distinct phases. The first phase releases 70% of the drug in the proximal duodenum, providing conventional delayed release, while the second phase releases the remaining 30% in the stomach environment, extending acid suppression. A randomized, open-label, two-way crossover bioequivalence study compared Esomeprazole Biphasic Micro Pellets Tablets (40 mg) with Nexium 40 mg gastro-resistant tablets. Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax, Tmax, Kel, t1/2) were assessed in healthy adult males under fasting conditions using non-compartmental analysis. The study demonstrated bioequivalence with 90% confidence intervals for Esomeprazole within acceptance criteria for Cmax, AUC0-t, and AUC0-inf. This randomized, open-label, two-treatment, two-period crossover study compared the bioequivalence of 40 mg Esomeprazole Biphasic MUPS tablets to Nexium in healthy adults. Blood samples were collected at 21 time points over 24 hours and analyzed using LC/MS/MS. Both formulations reached peak plasma concentrations (Cmax) at 3 hours, with Esomeprazole Biphasic MUPS showing an additional peak at 4 hours and sustained higher levels until 16 hours. The AUC0-t and AUC0-inf for Esomeprazole Biphasic MUPS were 5711.549 ng/mL and 5751.938 ng/mL, respectively, compared to 5615.535 ng/mL for both parameters with Nexium. Cmax was 1416.570 ng/mL for Esomeprazole Biphasic MUPS versus 1670.887 ng/mL for Nexium. Esomeprazole Biphasic MUPS provided 17.3% higher drug availability between 4 and 16 hours, suggesting a longer mean residence time and extended acid suppression compared to Nexium. In conclusion, Esomeprazole Biphasic Micro Pellets Tablets exhibited enhanced absorption characteristics and demonstrated bioequivalence to Nexium. The formulation was well-tolerated and provided extended acid suppression, offering potential clinical advantages in the management of acid-related disorders.

Keywords: Esomeprazole, MUPS, Proton Pump Inhibitor (PPI), gastroesophageal reflux disease (GERD), Quality by Design (QbD), Formulation Development, Bioequivalence.