Compare and PASS - Fast screening of oral dosage forms for bioequivalence probability with the COMPASS software

COMPASS is a novel tool for predicting the in vivo similarity of immediate-release oral dosage forms. It bridges the gap between straightforward but purely mathematical f2 factor-based assessment of dissolution profiles and complex physiologically-based pharmacokinetic simulations. This Python-based program uses semi-mechanistic modeling to evaluate the relative differences between key pharmacokinetic endpoint parameters - C_max and AUC - at variable gastric emptying rate (kGE) and the housekeeping wave time (GET) under fasting conditions. Through a graphical interface the user uploads dissolution results and fits a modified Noyes-Whitney model. Then, after providing the pharmacokinetic absorption and disposition parameters (effective permeability, clearances and distribution volumes) of a given drug, COMPASS generates an interactive report with predicted differences for C_max and AUC as a function of kGE and GET (3D surface plot), as well as the full plasma concentration-time profiles. Using a dataset comprising 15 formulations (reference and test pairs) containing 11 different drug substances (BCS class I - IV), we determined the measures for discriminating between bioequivalent vs. nonbioequivalent test and reference pairs. We also found that COMPASS-based bioequivalence predictions were similar as those from physiologically-based pharmacokinetic models built in commercially available software. Therefore, COMPASS can support the development of immediate-release dosage forms by fast screening of formulations for bioequivalence/non-bioequivalence, particularly in the early stages, thereby boosting the success rate of clinical trials.