Assessing the feasibility of using an animal model for in vivo taste assessment of pharmaceutical compounds and formulations

Palatability is crucial for patient acceptability and compliance with prescribed medicines, in particular with paediatric patients. However, palatability studies with human taste panels can only be carried out during advanced drug development phases when toxicology data of the drug are available. Thus, there is a great need to develop a method to assess the taste of pharmaceutical compounds and formulations at early stages of drug development. This could enable to identify taste aversive compounds at screening stages of pharmaceutical development and optimise taste-masking approaches for ensuring patient compliance. The feasibility of using the rat Brief-Access Taste Aversion (BATA) model for taste assessment of pharmaceutical compounds and formulations was investigated. The rat BATA model is a taste assessment technique where mildly water-deprived rats are presented with several solutions for few seconds; the taste is assessed by the number of licks recorded with a lickometer. Preliminary experiments conducted with the rat BATA model showed that the model was capable to detect the aversive taste of structurally different compounds having different physico-chemical properties and several levels of aversiveness. They also enabled to identify experimental parameters that were optimised with the help of a Design of Experiments. The analysis of the data provided by the BATA experiments was explored and a new Emax model was developed to determine the IC50 value enabling the quantification of the oral aversiveness of each test compound. Five model drugs were assessed by a human taste panel; a strong correlation was found between the two in vivo taste assessment methods. The levels at which several sweeteners commonly used in paediatric formulations could be assessed with the applied model. Finally, it was found that juvenile rats could be a model predicting more naïve taste in children