In vitro drug testing for mechanistic studies and accurate in vivo bioavailability predictions.

In recent years, a variety of in vitro tools with different levels of complexity and biological relevance have emerged in pharmaceutical research and development, driven by increasing ethical and environmental concerns. In our study, we introduce one such tool, the Meso-fluidic Chip for Permeability Assessment (MCPA), for the first time.

The MCPA combines an artificial barrier, known as PermeaPad®, with MIVO® organ-on-chip platform, along with real-time automated concentration measurements. This integration results
in a sustainable and straightforward method for permeation testing. The system offers three key physiological features: a biomimetic membrane, an optimal membrane interfacial area-to-donor-volume ratio (A/V), and physiological flow on the acceptor/basolateral side. These characteristics make the MCPA an ideal platform for mechanistic studies and accurate predictions of in vivo bioavailability.

We validated the method using various drug compounds under both unstirred and stirred donor conditions. Additionally, we explored its potential for dissolution/permeation testing on crystalline adducts of a BCS class III/I drug (pyrazinamide) and amorphous solid dispersions of a BCS class II/IV drug (hydrocortisone). The results demonstrated high reproducibility and highlighted the method’s ability to evaluate the performance of enabling formulations, potentially predicting in vivo performance.

We believe that with further development, the MCPA will become a valuable in vitro tool, contributing to sustainability in pharmaceutics by refining, reducing, and replacing animal testing in early-stage drug development.