Current Computational Approaches to Support Pharmaceutical Solid Form Selection

This contribution reviews current computational approaches to complement polymorph screening in the pharmaceutical industry by facilitating an assessment of the likelihood of a missed stable form. The focus is given to such methods as crystal structure prediction, hydrogen bonding propensity analyses, and rational solvent selection for stable form screening. Special consideration is given to the advantages and limitations of each method. It is suggested that, due to the outlined limitations, an in silico risk assessment of solid form selection in the pharmaceutical industry should be based on a combination of all of these approaches. A detailed application of these computational tools in the pharmaceutical industry is illustrated on a selective dual ALK and c-MET inhibitor crizotinib (trade name Xalkori) and on a VEGF inhibitor axitinib (trade name Inlyta).