A quality by design strategy for cocrystal design based on novel computational and experimental screening strategies: part A

Abstract While pharmaceutical Cocrystals have long been acknowledged as a promising method of enhancing a drugs bioavailability, they have not yet experienced widespread industrial adoption on the same scale as other multi-component drugs, such as salts and amorphous solid dispersions. This is partly due to the lack of a being no definitive screening strategy to identify suitable coformers, with the most cocrystal screening strategies heavily relying on trial and error approaches, or through utilizing a multiple and often conflicting, computational screening techniques combined with high material consumption experimental techniques. From the perspective of industry, this can often lead to high material waste and increased costs, encouraging the prioritization of more traditional bioenhancement techniques. Here we present a strategy for the selection of multicomponent systems involving computational modelling for screening of drug– former pairs based on a combination of molecular complementarity and H-bond propensity screening. Jet dispensing printing technology is co-opted as a mechanism for High-Throughput Screening (HTS) of different stoichiometric ratios, as a low material consumption screening strategy. This strategy is presented herein as a Quality by Design (QbD) crystal engineering approach, combined with experimental screening methods to produce cocrystals of a novel 5-Lipoxygenase (5‐LO) inhibitor, PF-04191834 (PF4). Through this methodology, three new cocrystals were indicated for PF4, confirmed via DSC and XRPD, from less than 50 mg of original testing material. Part B of this study will demonstrate the scalability of this technique continuous extrusion. Graphical Abstract