Comparison of Phosphate and Bicarbonate Buffer Solutions as Dissolution Test Media for Predicting Bioequivalence of Febuxostat Formulation.

Abstract

The purpose of the present study was to compare phosphate buffer (PPB) and bicarbonate buffer (BCB) solutions as dissolution test media for predicting the bioequivalence (BE) of an immediate-release (IR) formulation. Febuxostat was used as a model of free acid drugs. One reference formulation (RF) and three test formulations (TF) were employed in this study. The clinical BE studies involved 18 to 24 healthy adult volunteers. Each formulation was orally administered in the fasted state. The compendial paddle apparatus was used for the dissolution tests (500 mL, 37 °C, 25 or 50 rpm). BCB (10 mM, pH 6.8, 140 mM NaCl) and PPB (2.5 to 25 mM, pH 6.8, 140 mM NaCl) were used as dissolution media. The pH value of BCB was maintained by the floating lid method. In the clinical BE studies, two TFs were BE to RF, whereas one TF was non-BE. At a paddle speed of 50 rpm, RF and TFs showed little or no difference in the dissolution profiles in all buffer solutions. At 25 rpm, the dissolution profiles in 2.5 mM PPB and 10 mM BCB were consistent with the clinical BE results. The in vitro-in vivo correlation between C_max ratio and dissolved% ratio at each time point was highest for 10 mM BCB at 25 rpm. These results suggest that the use of BCB increases the BE predictability of dissolution tests.