(606a) The Importance of Solid-State Modeling in Drug Development

The properties of organic solids, including physiochemical stability, solubility, and mechanical behavior, are drastically affected by the way in which molecules arrange themselves. One fundamental component of small-molecule drug development is to determine and characterize the crystalline forms (or polymorphs) of the active pharmaceutical ingredient (API), as well as its solvated forms, and choose one that possesses an optimal set of properties. When the pure API or its solvates cannot form crystal structures with suitable properties (e.g. sufficient solubility), alternative solid forms, like salts or cocrystals, can be explored to strike an optimal balance. Thorough experimental form screens are costly, laborious and yet not guaranteed to find all the important solid phases. Solid-state modeling can be of tremendous value to drug development, as it can help right-size the experimental effort, assess the presence or absence of risks associated with the chosen form and direct experimental work towards the most relevant threats and opportunities. In this presentation, we show how solid-state modeling, including crystal structure prediction and virtual cocrystal screening, can support drug development projects, and how its integration with experimental efforts has made it a vital component in the solid form selection process.