On 27 August at 10:15 Mare Oja will defend her doctoral thesis „Experimental investigation and modelling of pH profiles for effective membrane permeability of drug substances“.
VanemteadSeniro Research Fellow Uko Maran (PhD), Institute of Chemisrty, University of Tartu
Prof. Dr Johann Gasteiger, Friedrich-Alexander University Erlangan-Nuremberg , Department of Chemistry and Pharmacy, Germany
Drugs are mainly administrated orally, like tablets, capsules, and solution. Developing orally administrated drugs, it is important to analyse the process in the gastrointestinal tract, i.e. what human organism do with the drug. Gastrointestinal tract is complex system, which includes areas with different properties. One of them is acidity/basicity, which varies from very acidic (stomach) to basic (colon) and it depends on the fasted and fed state. The environment in the gastrointestinal tract is influencing the properties of drug substances. For example, at what conditions and in what part of the gastrointestinal tract the drug substance can cross the intestinal barrier to arrive to the blood circulation. This process, i.e. a permeability, is the main topic of the current thesis.
In the early stage of drug discovery, the permeability is mainly analysed at neutral environment, although part of such environment in the gastrointestinal tract is very rare. This can be one reason why very many drug candidates fail during the later stage of drug discovery. Within current thesis, permeability was measured and analysed in the various acidity/basicity conditions, which are similar to the gastrointestinal tract. The results show that considering both acidic and basic environment can improve description of the permeability in the gastrointestinal tract.
Often, new drug candidates are not yet synthesised and thus these candidates cannot analyse experimentally. In this situation, computational methods, like prediction models, which take account structure of drug candidate, can be used for predicting permeability. During the thesis, different prediction models have been developed, which can be used to predict permeability at various conditions and in the various parts or over the gastrointestinal tract. These models can be used to select out best new drug candidates for the oral administration, but also for the food, cosmetic, and chemistry industries to analyse influence of the chemicals to the human without animal testing.