WP leaders: James Butler GlaxoSmithKline Research and Development Ltd and Patrick Augustijns Kathlieke Universiteit Leuven.
The objectives of WP2 are:
- To establish a functional array of in vitro tools for formulation evaluation, with maximised in vivo predictive power
- To develop a decision tree for selecting the most appropriate in vitro model(s) for a given drug/formulation/prandial state combination.
The tools and decision tree will be aimed at maximizing the biorelevance (and thus predictive power) whilst retaining simplicity (and thus ease of use) of the recommended in vitro tests.
Two synergistic approaches will allow the general objectives to be achieved: (1) systematic testing and validation of existing, optimised and new in vitro models, and (2) translation of improved understanding of underlying gastrointestinal processes into optimised and/or new biorelevant in vitro models.
1. Testing and validating in vitro models
To resolve the insufficient and anecdotal validation of many currently available in vitro models, the existing, optimised and new models will be systematically challenged to predict the known in vivo performance (human PK data) of a wide selection of IR and MR formulations.
2. Developing improved and novel biorelevant in vitro models
The extensive testing of in vitro models is likely to reveal gaps in the current array of in vivo predictive tools. Improved or novel models will be developed based on knowledge on intraluminal drug and formulation behaviour in vivo, either from the literature or arising from studies in WP3. This approach ensures the development of physiologically relevant, rather than purely outcome-driven, simulation models. In addition, the in vitro models for formulation evaluation will be developed in close collaboration with the API profiling performed in WP1.