An integrated approach combining experimental, informatics and energetic methods for solid form derisking of...

Area of Science:

• Crystallography
• Pharmaceutical Sciences
• Computational Chemistry

Background:

• Predicting and analyzing crystal packing in small-molecule drug candidates is complex.
• Identifying thermodynamically stable solid forms is crucial during drug development.
• Informatics-based risk assessments, termed Solid Form Health Checks, aid in digital workflows.

Purpose of the Study:

• To analyze competing polymorphs of PF-06282999, a myeloperoxidase (MPO) inhibitor.
• To demonstrate a combined experimental, informatics, and energetic calculation approach for solid form assessment.
• To ensure robust solid form derisking and selection for drug candidates.

Main Methods:

• Utilized a combined approach integrating experimental data, informatics tools, and energetic calculations.
• Analyzed four competing polymorphs of PF-06282999.
• Investigated the conformational flexibility and hydrogen bonding networks of the MPO inhibitor.

Main Results:

• The combined approach provided a comprehensive understanding of solid form structure and properties.
• Detailed analysis of PF-06282999 polymorphs was achieved.
• Effective derisking and selection of the optimal solid form were facilitated.

Conclusions:

• A multi-faceted approach is effective for analyzing complex small-molecule solid forms.
• Solid Form Health Checks enhance the understanding and selection of drug candidates.
• This methodology ensures the development of stable and performant drug products.