Bicarbonate Buffer Dissolution Test Using the Floating Lid Method: Inter-Laboratory Reproducibility of pH Maintenance.

Abstract

Bicarbonate buffer (BCB) has been difficult to use in conventional dissolution tests because its pH rapidly increases as CO₂ escapes from the air-water interface. Recently, the floating lid method was introduced as a convenient method for using BCB in dissolution tests. This study aimed to confirm the inter-laboratory reproducibility of pH maintenance of BCB using the floating lid method for both paddle and flow-through cell (FTC) methods. Three pharmaceutical companies and 1 academic research institute participated in this study. A BCB solution (pH 6.5, 15 mM) was employed as the test solution. In the paddle method, the pH values of BCB rapidly increased without the floating lid. The pH change (ΔpH) at 6 h ranged from +1.66 to +1.82 (50 rpm) and +1.96 to +2.02 (100 rpm). The floating lid effectively maintained the pH values in all laboratories, with ΔpH ranging from +0.13 to +0.17 (50 rpm) and +0.21 to +0.25 (100 rpm). The standard deviation of ΔpH was within 0.05 at both 50 and 100 rpm. Similarly, in the FTC method, without the floating lid, ΔpH ranged from +1.71 to +1.77 (reservoir), +1.59 to +1.72 (FTC), and +1.73 to +1.76 (sampling tube). With the floating lid, ΔpH ranged from +0.05 to +0.10 (reservoir), +0.05 to +0.09 (FTC), and +0.26 to +0.39 (sampling tube). The standard deviation of ΔpH was within 0.05. In conclusion, the inter-laboratory reproducibility of pH maintenance of BCB using the floating lid method was confirmed for both the paddle and FTC methods.