It is important to consider drug-excipient interactions and the mechanisms of dissolution, migration, and absorption in clinical practice. However, the complexity of drug-excipient interactions makes their evaluation difficult. To address this, experimental animals are used as models. However, evaluation in animal models is also complicated. Although in vitro models do not generally share biological similarities with humans, they allow the examination of complicated phenomena in a simplified form. Thus, in vitro methodologies can reduce the use of experimental animals in studies of the mechanisms of drug-excipient interactions. We developed a novel in vitro gastrointestinal (GI) absorption model, which can evaluate the dissolution, migration, and membrane permeation of a drug. Drugs, excipients, and solution media are allowed to leave the experimental system gradually in this model. We used methylene blue trihydrate as a cationic drug and sodium alginate as an anionic excipient to investigate the influence of the drug-excipient interaction. This GI absorption model can simultaneously evaluate and quantify the dissolution and membrane permeation processes. In addition, it can assess the dynamic changes in the dissolution and permeation processes associated with the migration of a drug with excipients.