Biorelevant Media and Relevance in Current Time

The first biorelevant media were introduced a good quarter of a century ago and have since been a success story, particularly in the development of formulations for poorly soluble drugs. The first candidates were developed to simulate intraluminal conditions in the upper gastrointestinal tract of fasting adults in a clinical study setting. This was quickly followed by the first media to simulate postprandial conditions in the small intestine and stomach in adults under typical conditions of a fed state clinical study, i.e. after ingestion of an “FDA standard breakfast”. When designing the media, special consideration was given to various physicochemical properties of the luminal contents, such as the pH value, buffer capacity, surface tension, osmolality, ion composition and typical bile salt concentrations, because these factors can have a decisive impact on the in vivo solubility of poorly soluble drugs and, accordingly, on the amount of drug absorbed. In the meantime, some media have been updated based on the latest findings and the set of media has been completed with the first media to simulate conditions in the fasting and postprandial colon. In addition, biorelevant media have found their way into the pharmaceutical industry over the last two decades as an essential component of predictive in vitro tools for estimating the in vivo performance of oral dosage forms and are nowadays indispensable here. In addition to the meanwhile “classical” simulation of intraluminal conditions in fasting and postprandial young adults in clinical studies, there are currently a number of efforts to develop biorelevant media to simulate gastrointestinal conditions in specific patient populations. Last but not least, it should be emphasized that the media are now also meeting with a much higher regulatory acceptance, because in many cases the in vivo performance of dosage forms with poorly soluble drugs could be predicted very well by a combination of biorelevant in vitro release tests and physiologically based pharmacokinetic models. This presentation will provide an overview of biorelevant media, starting with the establishment of the first media and concluding with current applications to highlight the particular relevance of these media.