Authors: Rola Barcham (1), Eric Andres (1), Axel Huyard (1), Christophe Dini (1)
1 : Oroxcell, 102 avenue Gaston Roussel, 93230 Romainville, France
The BCS based regulatory biowaiver of clinical bioequivalence studies provides significant relief from the regulatory burden on the development of generic products as well as the ethical advantage of avoiding unnecessary exposure of healthy human volunteers. Over 50% of the world most used and essential oral, immediate-release drugs are estimated to fall into the BCS Class I and Class III classification, representing an enormous potential for companies developing generic formulations or managing the lifecycles of existing products to save money and time. In the context of in vitro studies, Caco-2 cell lines have become the most frequently used in vitro models to perform such studies.
The present work evaluates a novel primary human cell-based 3D organotypic small intestinal microtissues to be a potential pathway for evaluating in vitro bioequivalence, but also using formulated API to estimate the impact of formulation in promotion of absorption and to make comparison of adultversus pediatric forms which are currently in development, at doses corresponding to those employed in clinics. The permeability coefficients across the microtissues were determined for a panel of benchmark drugs with known human absorption.
The reference substances were accurately classified into low and high permeable drugs. The 3D organotypic Human small intestinal tissue model is eligible to elaborate a correlation curve according to BCS based biowaivers. The predicted fraction absorbed in human determined with the EpiIntestinal model was equivalent in both tested conditions, test adult form (capsule of 500 mg) vs. pediatric form (Sachet content of 500 mg). The object of this work is to give an insight into the added value that could bring the 3D organotypic Human small intestinal tissue model, over Caco-2 cells, for selecting appropriate formulations to improve systemic drug exposure or anticipate the impact of a change in formulation for generics or pediatric drug products.