Development of a Biorelevant Dissolution Test Using Bicarbonate Buffer and Apex Vessel to Predict Clinical...

Bioequivalence (BE) studies are essential for confirming therapeutic equivalence. However, current compendial dissolution tests do not necessarily provide a reliable prediction of clinical BE. We aimed to develop a biorelevant dissolution test that predicts clinical bioequivalence (BE). Three enteric-coated pellets of esomeprazole magnesium trihydrate (ECP-ESO), either clinically BE or non-BE (NBE), were evaluated. Dissolution tests were performed using the paddle method (pH 6.5 or 6.8, 25-100 rpm, 500 mL, 37°C). Biorelevant bicarbonate buffer (BCB) was used as a simulated intestinal fluid, with a floating lid applied to prevent CO₂ escape and maintain pH. Hydrodynamics that suppresses artifact cone formation (coning) were produced using an apex vessel (Apex-V). These biorelevant conditions were compared with the compendial phosphate buffer (PPB) and the round-bottom vessel (RB-V). RB-V is considered less biorelevant as it causes coning at the vessel bottom. When PPB and RB-V were used, BE and NBE formulations could not be distinguished. Substitution of RB-V with Apex-V eliminated coning but lacked discriminative power. This outcome was also observed with BCB and RB-V. Combining both BCB and Apex-V successfully differentiated between BE and NBE formulations, consistent with the clinical BE results. Dissolution testing using biorelevant BCB and Apex-V predicted the clinical BE/NBE of ECP-ESOs. The floating lid method enabled the practical use of BCB, while Apex-V prevented coning. This simple, yet biorelevant, dissolution test could help to predict clinical BE in formulation development.