Leveraging the use of in vitro and computational methods to support the development of enabling oral drug products: An InPharma commentary
Christos Reppas, Martin Kuentz, Annette Bauer‐Brandl, Sara Carlert, André Dallmann, Shirin Dietrich, Jennifer Dressman, Lotte Ejskjær, Sebastian Frechen, Matteo Guidetti, René Holm, Florentin Lukas Holzem, Εva Karlsson, Edmund Kostewicz, Shaida Panbachi, Felix Paulus, Malte Bøgh Senniksen, Cordula Stillhart, David B. Turner, Maria Vertzoni, Paul Vrenken, Laurin Zöller, Brendan T. Griffin, P J O’Dwyer
Abstract
Due to the strong tendency towards poorly soluble drugs in modern development pipelines, enabling drug formulations such as amorphous solid dispersions, cyclodextrins, co-crystals and lipid-based formulations are frequently applied to solubilize or generate supersaturation in gastrointestinal fluids, thus enhancing oral drug absorption. Although many innovative in vitro and in silico tools have been introduced in recent years to aid development of enabling formulations, significant knowledge gaps still exist with respect to how best to implement them. As a result, the development strategy for enabling formulations varies considerably within the industry and many elements of empiricism remain. The InPharma network aims to advance a mechanistic, animal-free approach to the assessment of drug developability. This commentary focuses current status and next steps that will be taken in InPharma to identify and fully utilize 'best practice' in vitro and in silico tools for use in physiologically based biopharmaceutic models.