Modeling Gastrointestinal Motility: The Multiple Moving Plug Model

The effects of drug solubility and permeability on drug dissolution and absorption kinetics are generally better understood than the effects of gastrointestinal motility. Historically, gastrointestinal motility has be modeled as a first-order process across a series of imaginary barriers separating continuous stationary compartments of fluid, even though it is known the the fluid in the gastrointestinal tract exists in discrete pockets of ever-changing fluid, both in terms of position and volume. The multiple moving plug model will be described that provides a new framework to model gastrointestinal motility. The multiple moving plug model is more realistic and compatible with existing dissolution modeling and could offer an improved prediction of the effects of gastrointestinal motility on drug dissolution and absorption kinetics. As gastrointestinal motility is highly variable, modeling it more accurately may lead to a better understanding and a greater regulatory acceptance of its impact on drug pharmacokinetics. Acceptance and adoption of the multiple moving plug model may also lead to the development of more relevant dissolution tests.