A toolbox for mimicking gastrointestinal conditions in children: Design and evaluation of biorelevant dissolution media for mimicking paediatric gastric- and small intestinal conditions.

The goal of the present work was to develop an in vitro toolbox to evaluate the oral administration of dosage forms to children of different age groups and under different administration conditions (fasted/fed). Based on current data on the gastrointestinal physiology of children, a set of new biorelevant media was designed to mimic the composition and physicochemical properties of resting gastric and resting small intestinal fluid in children of different age groups. In addition, guidelines were developed on how to generate fasted and fed state gastric and small intestinal fluids by combining these media with age-specific drinking volumes or portions of already established simulated paediatric breakfast meals, respectively. These fluids can simulate the conditions in the paediatric stomach and small intestine after administration of a dosage form in the fasting state or after a breakfast. The in vitro toolbox was evaluated using the example of pre-school children with a total of five paediatric medicines. Results from the corresponding set of in vitro studies highlight the importance of addressing patient-specific characteristics rather than downscaling existing adult in vitro models.