Towards a standard toolbox for compatibility testing of pediatric drug products: verification of standard vehicles for fruit juice, apple sauce, yogurt, and pudding through comparative biorelevant dissolution testing using pediatric furosemide mini-tablets

In vitro compatibility assessments are a valuable tool for the early identification of potential drug-vehicle interactions. To standardize such evaluations, a set of standard vehicles, also referred to as simVehicles (simJuice, simApplesauce, simYogurt, and simPudding) because they simulate the key physicochemical properties of commonly used pediatric dosing vehicles, was previously developed using a Design of Experiments (DoE) approach to replicate these properties while ensuring reproducibility under controlled conditions. The present study aimed to validate selected simVehicles through comparative in vitro dissolution experiments using pediatric furosemide mini-tablets as a model drug product. The simVehicles successfully reproduced the furosemide release behavior observed with the corresponding original vehicles, supporting their suitability for standardized compatibility testing. Analysis further confirmed pH and buffer capacity as key determinants of furosemide release, highlighting their dominant role across vehicle types. These findings also emphasize the limitations of relying on a single vehicle type and the importance of accounting for vehicle-related variability, including parameters not yet covered by the current model, such as viscosity. Overall, the developed simVehicles provide a robust, scalable, and broadly applicable approach for early-stage drug-vehicle compatibility assessment.