Development of pH shift bicarbonate buffer dissolution test using floating lid and its feasibility for evaluating enteric-coated tablet

The purpose of the present study was to develop a pH shift bicarbonate buffer (BCB) dissolution test using a floating lid and investigate its feasibility for the evaluation of enteric-coated (EC) tablets. Rabeprazole EC tablets (one branded and 7 generic products) were employed as model formulations. In the pH shift BCB dissolution test, a floating lid was used to avoid an increase in pH due to CO2 evaporation (JDDST 2021 (63), 102447). An HCl solution (0.01 N, pH 2.0, 500 mL) was first added to a compendial dissolution vessel. The solution surface was then covered by a floating lid. After 1 h, a concentrated bicarbonate solution (50 mL, 110 mM, pH 9.5) was added to shift the pH value to pH 6.5 (final bicarbonate concentration: 10 mM). Dissolution tests were also performed in BCB without the pH shift and in a phosphate buffer (PB). After the pH shift, the pH value was maintained at pH 6.5 ± 0.1 for 5 h. During the acidic pH stage, the EC tablets did not disintegrate except for one generic tablet. At pH 6.5 after the pH shift, the average disintegration time was 49 ± 26 min (N = 8), which roughly corresponded to the clinical Tmax. However, a quantitative in vitro - in vivo correlation about Tmax was not observed probably because of a large variation in Tmax. Pre-exposure to the acidic pH environment did not affect the disintegration time. In BCB, the dissolution profiles showed a large variation among the drug products. In contrast, in PB, all tablets rapidly disintegrated (13 ± 4 min (N = 8)). These results are in good agreement with the previous study using the CO2 gas bubbling method. Since the pH shift BCB dissolution test using a floating lid is easy, low-cost, and compatible with the compendial paddle dissolution test apparatus, it would be useful in practical formulation development.