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Updated: Jan 27, 2026
Author Spotlight: High-Throughput Screening to Obtain Crystal Hits for Protein Crystallography
Published on: March 10, 2023
Applications of In Silico Solvent Screening and an Interactive Web-Based Portal for Pharmaceutical Crystallization
Jeffrey S Tan1, Lori R Hilden1, Jeremy M Merritt1
1Eli Lilly and Company, Small Molecule Design and Development, Indianapolis, Indiana 46285.
Abstract:
In an effort to reduce development time and costs associated with active pharmaceutical ingredient process solvent selection and crystallization design, a tiered approach to crystallization solvent selection was developed that leverages different solubility modeling tools selected on the basis of available data and the intended use of the prediction. To facilitate easy access to routine solubility modeling functionality with a high level of automation and parallelization, a web-based in silico solvent-screening tool was also developed as well as a user interface to visualize and interpret the large number of predicted results. Examples are presented to illustrate the utility of the workflow and solvent-screening tool at various stages of development for a diverse range of crystallization processes. Implementation of the in silico solvent selection workflow has led to a ∼10× reduction in active pharmaceutical ingredient usage and 20% reduction in full-time employee time per project based on average after the first year.
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