The integration of solid-form informatics into solid-form selection.

Area of Science:

• Crystallography
• Drug Development
• Computational Chemistry

Background:

• Polymorphism, the ability of a solid material to exist in multiple crystalline forms, presents significant challenges in drug development.
• Selecting a stable, commercially viable solid form is crucial for drug efficacy and manufacturing.
• Structural informatics offers a powerful toolkit for predicting and managing solid-state properties.

Purpose of the Study:

• To illustrate the utility of structural informatics in evaluating polymorphism risks during drug development.
• To demonstrate how informatics aids in selecting appropriate commercial solid forms for drug candidates.
• To showcase the integration of computational methods with experimental studies for robust solid-state characterization.

Main Methods:

• Leveraging the Cambridge Structural Database (CSD) for extensive crystal structure data.
• Applying structural chemistry principles to analyze intermolecular geometries and hydrogen bonding propensities.
• Utilizing tools like the Solid Form Module of Mercury for polymorph stability assessment via Full Interaction Maps.

Main Results:

• Early identification of unusual supramolecular motifs in maraviroc guided polymorph screening.
• Analysis of drug candidate polymorphs highlighted the role of molecular conformation and intermolecular interactions in stability.
• Informatics confirmed a low polymorphism risk for the monomorphic crizotinib solid form.

Conclusions:

• Informatics-based structural analysis complements experimental data, deepening the understanding of drug substance properties.
• Risk assessment for polymorphism is enhanced by incorporating structural informatics insights.
• Rapid and straightforward informatics techniques facilitate timely evaluation of progressing drug candidates.