Current challenges and future perspectives in oral absorption research: An opinion of the UNGAP network

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research

Application of Method Suitability for Drug Permeability Classification

Experimental models of permeability in animals, excised tissues, cell monolayers, and artificial membranes are important during drug discovery and development as permeability is one of several factors affecting the intestinal absorption of oral drug products. The utility of these models is demonstrated by their ability to predict a drug’s in vivo intestinal absorption. Within the various permeability models, there are differences in the performance of the assays, along with variability in animal species, tissue sources, and cell types, resulting in a variety of experimental permeability values for the same drug among laboratories. This has led to a need for assay standardization within laboratories to ensure applicability in the drug development process. Method suitability provides a generalized approach to standardize and validate a permeability model within a laboratory. First, assay methodology is optimized and validated for its various experimental parameters along with acceptance criteria for the assay. Second, the suitability of the model is demonstrated by a rank order relationship between experimental permeability values and human extent of absorption of known model compounds. Lastly, standard compounds are employed to classify a test drug’s intestinal permeability and ensure assay reproducibility and quality. This review will provide examples of the different aspects method suitability for in situ (intestinal perfusions), ex vivo (everted intestinal sacs, diffusion chambers), and in vitro (cell monolayers, artificial membranes) experimental permeability models. Through assay standardization, reference standards, and acceptance criteria, method suitability assures the dependability of experimental data to predict a drug’s intestinal permeability during discovery, development, and regulatory application