This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 956851.

Prof. Christos Reppas

Christos Reppas is Professor in Pharmaceutics, Department of Pharmacy, National and Kapodistrian University of Athens (NKUA), Greece. He received his Pharmacy Degree from NKUA in 1982 and his PhD in 1986 in Pharmaceutical Sciences from the same University. From 1988 to 1989 he completed a postdoctoral fellowship in Pharmaceutics at the University of Michigan (USA). He joined NKUA in 1989 as a Lecturer.

He has held research positions with the University of London (UK), the University of Michigan (USA), Glaxo R&D (UK) and the University of Frankfurt/Main (Germany). Research interests focus to the effects of dosage form characteristics and of gastrointestinal physiology on intraluminal performance of xenobiotics and the development of in vitro tests that are predictive of the intraluminal dosage form and drug performance. He has supervised 13 completed PhD Theses. He is coauthor of more than 140 peer reviewed papers and chapters in international journals and books, two books in Biopharmaceutics and Drug Disposition and one patent (h-index 46). He is member of the editorial board of AAPS Journal, Journal of Pharmacy and Pharmacology, Biopharmaceutics and Drug Disposition and Journal of Drug Delivery Science and Technology. He is/has been PI in several EU funded training and research programs (OrBiTo, PEARRL, COLOTAN, InPharma, AGePOP) and one COST action (UNGAP, vice-chair).


Characteristics of contents of proximal colon: Implications for drug absorption and in vitro simulations

Drug absorption from the large intestine is of interest when considering the development of modified release products. Occasionally, it may also be useful for understanding the pharmacokinetic performance of poorly soluble active pharmaceutical ingredients (APIs), BCS Class II and Class IV APIs, which are administered in immediate release products, when drug absorption is incomplete in the upper intestine.

Compared with the small intestine, effective drug permeability in the large intestine appears to be decreased for low permeability drugs, not much for high permeability drugs. Therefore, if the drug is available for absorption, the long residence times in the large intestine may, at least partly, balance the lower effective epithelial surface area. For the drug to be available for absorption, it must be molecularly dispersed (dissolved) in the luminal contents and resist bacterial degradation. The limited free water volume and the increased bacterial content in distal regions of the large intestine make the proximal colon the primary area of interest for the absorption of drugs in the large intestine.

One issue in the investigation of the luminal environment in the proximal colon relates to the sampling methodology. Some physicochemical characteristics, such as luminal free water volumes and pH, could be evaluated with imaging techniques which are both non-invasive and involve little or no bowel preparation. Other characteristics, however, which are also of prime importance for the luminal drug/drug product performance, e.g. buffer capacity, viscosity, presence of solubilizing agents, osmolality, evaluation of the impact of microbiome on bacterial drug degradation require direct sampling from the region. Also, potential differences between populations, e.g. young vs older adults may impact the effectiveness of certain modified release products.

In the first part of this presentation, relevant data to date, collected from both imaging and direct sampling techniques are summarized.

In the second part, the usefulness of recent information on the luminal environment of the lower intestine of adults in the design of in vitro tests for the evaluation of dissolution in the region will be discussed. The impact of passive absorption of high dose low solubility drugs from the lower

intestine plasma profile will also be evaluated based on biorelevant dissolution data and physiologically based absorption modelling.