Mass Transport Analysis of the Enhanced Buffer Capacity of the Bicarbonate–CO2 Buffer in a Phase-Heterogenous System: Physiological and Pharmaceutical Significance

The bicarbonate buffer capacity is usually considered in a phase-homogeneous system, at equilibrium, with no CO 2 ransfer between the liquid buffer phase and another phase. However, typically, an in vitro bicarbonate buffer-based system is a phase-heterogeneous system, as it entails continuously sparging (bubbling) the dissolution medium with CO 2 in a gas mixture, at constant ratio, to maintain a constant partial pressure of CO 2 (g) and CO 2(aq) molarity at a prescribed value, with CO 2 diffusing freely between the gas and the aqueous phases. The human gastrointestinal tract is also a phase-heterogeneous system, with CO 2 diffusing across the mucosal membrane into the mesenteric arterial blood, which serves as a sink for CO 2 from the intestinal lumen. In this report, a mass transport analysis of the apparent buffer capacity of a phase-heterogeneous bicarbonate-CO 2 system is developed. It is shown that, most significantly, a phase-heterogeneous bicarbonate-CO 2 system can have a much higher buffer capacity than a phase-homogeneous system such that the buffer capacity is dependent on the bicarbonate concentration. It is double that of a phase-homogeneous system at the pH = p K a for a monoprotic buffer at the same concentration. This buffer capacity enhancement increases hyperbolically with pH above the p K a , thus providing a much stronger buffering to keep the pH in the physiologically neutral range. The buffer capacity will be dependent on the bicarbonate molarity (which in vivo will depend on the bicarbonate secretion rate) and not the pH of the luminal fluid. Further, there is no conjugate acid accumulation as a result of bicarbonate neutralization, since the resulting carbonic acid (H 2 CO 3 ) rapidly dehydrates producing CO 2 and H 2 O. The mass transport analysis developed in this report is further supported by in vitro experimental results. This enhanced bicarbonate buffer capacity in a phase-heterogeneous system is of physiological significance as well as significant for the dissolution and absorption of ionizable drugs.