Shifting the Focus from Dissolution to Permeation: Introducing the Meso-fluidic Chip for Permeability Assessment (MCPA)

Martina M Tzanova, Bjarke Strøm Larsen, Rebecca Birolo, Sara Cignolini, Ingunn Tho, Michele R Chierotti, Beatrice Perissutti, Silvia Scaglione, Paul C Stein, Marianne Hiorth, Massimiliano Pio Di Cagno*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

In response to the growing ethical and environmental concerns associated with animal testing, numerous in vitro tools of varying complexity and biorelevance have been developed and adopted in pharmaceutical research and development. In this work, we present one of these tools, i.e., the Meso-fluidic Chip for Permeability Assessment (MCPA), for the first time. The MCPA combines an artificial barrier (PermeaPad®) with an organ-on-chip device (MIVO®) and real-time automated concentration measurements, to yield a sustainable, yet effortless method for permeation testing. The system offers three major physiological aspects, i.e., a biomimetic membrane, an optimal membrane interfacial area-to-donor-volume-ratio (A/V) and a physiological flow on the acceptor/basolateral side, which makes the MPCA an ideal candidate for mechanistic studies and excellent in vivo bioavailability predictions. We validated the method with a handful of assorted drug compounds in unstirred and stirred donor conditions, before exploring its applicability as a tool for dissolution/permeation testing on a BCS class III/I drug (pyrazinamide) crystalline adducts and BCS class II/IV (hydrocortisone) amorphous solid dispersions. The results were highly reproducible and clearly displayed the method's potential for evaluating the performance of enabling formulations, and possibly even predicting in vivo performance. We believe that, upon further development, the MCPA will serve as a useful in vitro tool that could push sustainability into pharmaceutics by refining, reducing and replacing animal testing in early-stage drug development.

Original languageEnglish
JournalJournal of Pharmaceutical Sciences
Volume113
Issue number5
Pages (from-to)1319-1329
ISSN0022-3549
DOIs
Publication statusE-pub ahead of print - 16. Dec 2023

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