Towards exhaustive and automated high-throughput screening for crystalline polymorphs

Area of Science:

• Solid-state chemistry
• Materials science
• Crystallography

Background:

• Exhaustive screening for crystal polymorphism is challenging.
• Polymer-induced heteronucleation (PIHn) offers kinetic access to diverse polymorphs.
• Current methods lack high-throughput capabilities for early-stage drug development.

Discussion:

• A high-density format of PIHn, utilizing 288 distinct polymers on a single substrate, enables thousands of automated crystallizations.
• This method requires only milligrams of sample, making it suitable for preclinical candidates.
• The approach facilitates the determination of polymorphism propensity early in the drug development pipeline.

Key Insights:

• Demonstrated PIHn's efficacy with four pharmaceutically relevant compounds: acetaminophen, tolfenamic acid, ROY, and curcumin.
• The high-density array significantly enhances screening efficiency and reduces sample requirements.
• Accelerated polymorph discovery is crucial for optimizing drug properties and development timelines.

Outlook:

• This technology can be applied to a broader range of pharmaceutical targets.
• Further optimization of PIHn formats could lead to even greater screening capabilities.
• Early identification of polymorphism will streamline drug development and improve compound selection.