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Christer Tannergren, PhD

Principal Scientist in Biopharmaceutics at Oral Product Development, Pharmaceutical Technology & Development, AstraZeneca Gothenburg, Sweden.

He received his PhD in Biopharmaceutics at the Department of Pharmacy, Uppsala University, Sweden in 2004. He has held various Biopharmaceutics expert positions and Product Development Lead roles since joining AstraZeneca in 2003. His main areas of research interest include physiologically based biopharmaceutics modelling and regional intestinal absorption/bioavailability as well as development of low solubility and Modified Release drug products. He has co-supervised 3 PhD students and is author of 35 peer-reviewed papers as well as inventor of 1 formulation patent.

Abstract

 

Industrial aspects on assessment & prediction of colon absorption – current state & challenges​

Sufficient colon absorption is generally a prerequisite for successful extended/modified release (ER/MR) product development. The physiological characteristics of colon may constitute a major barrier to membrane transport, drug dissolution and luminal stability in the colon and limited colon absorption is a main reason why development of ER/MR drug products may fail. Consequently, it is highly desirable to understand and be able to predict the extent of colon absorption in humans.

There are several in vivo (preclinical and clinical), in vitro and in silico techniques available to assess different aspects of colon absorption. The current in vivo techniques mainly include various remote control capsule, intubation and colonoscopy approaches to investigate the relative bioavailability between oral/small intestinal and colon administration in humans or dogs. In vitro permeability classification according to high/low permeability class has been shown useful to predict complete/incomplete colon absorption.

Also, a clear sigmoidal relationship between the apparent permeability and the fraction absorbed after colon administration in humans has been demonstrated for both the Caco-2 and the human excised colon tissue models. There is currently limited understanding of the in vivo impact of solubility/dissolution on the colon absorption of drugs, however recent characterization of the ascending colon contents and newly developed simulated colonic fluid medium may improve the understanding in this area. In vitro methods to investigate bacteria-mediated luminal degradation kinetics in the colon include the use human proximal colonic fluid or faecal homogenates. The current colon models in the available mechanistic in silico physiologically based biopharmaceutics models show limited ability to predict the rate and extent of colon absorption of drugs in humans.