Prof. Dr. Jennifer Dressman
Avoiding experiments in animals using dissolution-based approaches
Talk Title:
About Speaker
Fraunhofer Institute of Translation Medicine and Pharmacology
Professor Jennifer Dressman, who retired as Professor of Pharmaceutical Technology at the Goethe University in 2021, now leads a formulation group at the Fraunhofer Institute of Translation Medicine and Pharmacology in Frankfurt am Main, Germany. Professor Dressman’s research interests focus principally on predicting the in vivo performance of drugs and dosage forms after oral administration. She is best known for pioneering the use of biorelevant dissolution testing and her contributions to combining dissolution testing with physiologically based pharmacokinetic modelling in order to achieve quantitative predictions of oral drug absorption.
Abstract
The EU project InPharma“ (https://www.inpharma-network.eu/) explores setting up a fully integrated, animal-free end-to-end modeling approach to the development of oral drug formulations. A key part of this approach is to identify dissolution methods which can reflect product performance in the GI tract under a variety of dosaing conditions. This presentation focuses on three areas in which a customized dissolution test is required: a) when acid-reducing agents (ARA) are administered, b) when the dosage form is administered with a meal and c) drug release in overdose situations.
By combining dissolution results in customized ARA media with physiological based pharmacokinetic (PBPK) models, changes in the pharmacokinetics of weakly basic drugs can be simulated well. The key take-home message is that low-buffer capacity media are required to reflect H2-receptor antagonist/PPI therapy..
A new series of media (FedGAS) has been introduced to represent fed state conditions in the stomach to help understanding of how a high-fat meal, such as those used in food effect studies, can influence bioavailability. By combining the dissolution behaviour of two differently formulated amorphous solid dispersions of itraconazole with PBPK mdodeling, it was possible to distinguish between positive and negative food effects.
Lastly, overdosing has become a major problem in the USA and abroad. To better treat those who overdose, it is important to understand how drug release in vivo is affected when multiple dosage units are ingested. For this, we devised a dissolution method in USP 3 equipment to mimic drug release from up to 50 units and compared results for four marketed products of acetaminophen (IR tablets, hard capsules, soft capsules, and ER tablets), in some cases, clumping of the dosage units together led to slow and incomplete release. The method offers a first step to predicting plasma profiles from drugs, such as paracetamol, that are often involved in overdose cases.