Evaluating experimental, knowledge-based and computational cocrystal screening methods to advance drug-drug cocrystal fixed-dose combination development

Fixed-dose combinations (FDCs) offer significant advantages to patients and the pharmaceutical industry alike through improved dissolution profiles, synergistic effects and extended patent lifetimes. Identifying whether two active pharmaceutical ingredients have the potential to form a drug-drug cocrystal (DDC) or interact is an essential step in determining the most suitable type of FDC to formulate. The lack of coherent strategies to determine if two active pharmaceutical ingredients that can be co-administered can form a cocrystal, has significantly impacted DDC commercialisation. This review aims to accelerate the development of FDCs and DDCs by evaluating existing experimental, knowledge-based and computational cocrystal screening methods; the background of their development, their application in screening for cocrystals and DDCs, and their limitations are discussed. The evaluation provided in this review will act as a guide for selecting suitable screening methods to accelerate FDC development.