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High-Throughput Screening to Obtain Crystal Hits for Protein Crystallography
Published on: March 10, 2023
Medium-throughput hydrate screening using the Crystal 16™
Anand Sistla1, Yi Wu, Penney Khamphavong
1Research Enabling Group, Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California 92121, USA. Anand.Sistla@Pfizer.com
Pharmaceutical Development and Technology
|January 22, 2010
Summary
Early identification of compound hydrate formation is crucial in drug development. A new screening method using Crystal 16™ efficiently predicts hydrate propensity, aiding compound selection and process control.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
- Drug Development
Background:
- Hydrates significantly impact compound solubility and exposure, often forming during pharmaceutical manufacturing.
- Early detection of hydrate formation propensity is vital for process optimization and compound selection.
Purpose of the Study:
- To develop and validate a medium-throughput screening method for assessing compound hydrate formation propensity.
- To identify optimal conditions for hydrate screening using the Crystal 16™ system.
Main Methods:
- A novel screening approach utilizing the Crystal 16™ instrument with an accelerated thermal cycling protocol.
- Testing was performed in a mixed solvent system (acetonitrile-water) with nine diverse compounds.
Main Results:
- The developed method successfully identified hydrate formation for seven known hydrate-forming compounds and correctly predicted no hydrate formation for two others.
- An optimized thermal cycle (25°C→40°C→5°C→25°C over 6 hours) and solvent system were established.
- The method requires a minimal sample amount (15-20 mg) for analysis.
Conclusions:
- The Crystal 16™-based screening method provides a rapid and reliable means to assess hydrate formation propensity early in drug development.
- This technique supports informed decisions in late lead-development and early candidate selection phases.
- Implementing this method can prevent downstream processing issues related to unexpected hydrate formation.
