The Fluid Dynamics of the Dissolution of an Oral Drug in the Human Stomach

The oral route is used most frequently for drug administration in human due to its safety, reduced cost, and high degree of patient compliance, but it is also the most complex way for an active pharmaceutical ingredient to enter the body. This complexity is because drug absorption via the gastrointestinal tract depends not only on factors related to the drug and its formulation, but also the contents and motility of the stomach. Also, the dynamic physiological environment of the stomach generates complex pill trajectories and non-uniform rate of dissolution and emptying of the drug into the duodenum, which potentially affects drug bioavailability. These issues pose several challenges to the design of drug delivery systems from R&D, clinical, and regulatory perspectives. These are particularly relevant for disease conditions that are associated with alterations in the anatomy and/or physiology of the stomach as current clinical approaches to assess the efficacy of oral drugs are limited in their ability to elucidate the relationship between bioavailability and altered stomach. We employ "StomachSim", a CFD model of human stomach, to investigate the effect of body posture and stomach motility on drug bioavailability and understand the fluid-dynamic mechanisms of drug dissolution.