Mass Transport Analysis of the Enhanced Buffer Capacity of the Bicarbonate–CO2Buffer 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 CO2transfer between the liquid buffer phase and another phase. However, typically, an in vitrobicarbonate buffer-based system is a phase-heterogeneous system, as it entails continuously sparging (bubbling) the dissolution medium with CO2in a gas mixture, at constant ratio, to maintain a constant partial pressure of CO2 (g)and CO2(aq)molarity at a prescribed value, with CO2diffusing freely between the gas and the aqueous phases. The human gastrointestinal tract is also a phase-heterogeneous system, with CO2diffusing across the mucosal membrane into the mesenteric arterial blood, which serves as a sink for CO2from the intestinal lumen. In this report, a mass transport analysis of the apparent buffer capacity of a phase-heterogeneous bicarbonate–CO2system is developed. It is shown that, most significantly, a phase-heterogeneous bicarbonate–CO2system 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 = pKafor a monoprotic buffer at the same concentration. This buffer capacity enhancement increases hyperbolically with pH above the pKa, 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 vivowill 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 (H2CO3) rapidly dehydrates producing CO2and H2O. The mass transport analysis developed in this report is further supported by in vitroexperimental 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.