In order to achieve the desired effect in vivo, drugs taken orally must first be dissolved in the gastrointestinal tract. With the majority of the commercially available drugs having acidic and/or basic groups, ionization and intestinal buffering are important factors underlying adequate dissolution and, accordingly, bioavailability. The aim of this work was therefore to develop a dissolution model that properly takes these factors into account when dealing with the intestinal bicarbonate buffer. Based on the assumptions that, during dissolution, steady state is reached instantaneously, all the reactions are at equilibrium save for the interconversion between H