The optimal use of in-vitro tools for the prediction of in-vivo oral dosage form behaviour

Since the early 1970’s an ongoing debate in pharmaceutical sciences has been how (and when) can relatively simple models (in-vitro and more recently, in-silico) be used to reliably predict in-vivo performance? Secondary questions to this are: How complex does modelling need to be to identify the best formulation option for first time in human (FTIH) dosing of a new oral drug? When can dissolution using simple pharmacopeial methods be used to predict oral drug performance? When is it necessary to use a more complex dissolution system that better reflects the fluid dynamics in the GI tract? For extended drug release, when is it necessary to use, in addition to the dissolution data other factors (e. g. changes in drug permeability with regional transit for example) in order to successfully predict in-vivo performance from in-vitro dissolution? The work presented here tests the hypothesis that simple biorelevant media, either for solubility determination or as a dissolution test media, in combination with some basic information on permeability and dose, can be used predict in-vivo performance of a reasonable range of oral drugs and formulations without the need for complex, novel dissolution test equipment or complex modelling.