A multiscale absorption and transit model for oral drug delivery: Formulation and applications during fasting conditions.

Most Food and Drug Administration (FDA)-approved drugs are administered orally, despite the complex process of oral drug absorption that is difficult to analyze experimentally. Oral bioavailability is dependent on the drug compound as well as the physiological and anatomical states of the user. Thus, computational models have emerged to mechanistically capture and predict the oral absorption process. The current models are generally 0D compartmental models and are limited by (a) simplified physiological characteristics of the gastrointestinal tract (GIT), (b) semiempirical/analytical dissolution profiles of the tested drugs, (c) incorrect absorption for some drug BCS classes (class IIa, for example), (d) GITs size variability among population, (e) incorrectly predicting the absorption of drugs that are GIT target specific, and (f) erroneous mixing in the domain. In this study, we have developed a multiscale absorption and transit (MAT) toolkit to simulate the dissolution, transport, absorption, distribution, metabolism, and elimination of orally administered drugs in the human GIT at multiple levels. MAT was constructed by integrating the spatially accurate first-principles driven high-fidelity drug transport, dissolution, and absorption model in the human stomach and GIT using our recently published quasi-3D (Q3D) framework. The process integrated the multilayer intestine physiologically based pharmacokinetics models with the whole-body compartmental models to predict the systemic pharmacokinetics of oral drugs. The computational results showed that this multiscale tool was able to match the experimental concentration results (individual and population) better than the traditional compartmental models. Ultimately, MAT will be developed into a commercial product to meet urgent demands from pharmaceutical and biomedical industries.