Towards Exhaustive and Automated High-Throughput Screening for Crystalline Polymorphs
| Autor: | Laura Y. Pfund, Adam J. Matzger |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Letter
Polymers Chemistry High-throughput screening Nanotechnology 02 engineering and technology General Chemistry General Medicine pharmaceuticals 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences High-Throughput Screening Assays 0104 chemical sciences Automation Drug development Raman spectroscopy Crystallization polymer-induced heteronucleation 0210 nano-technology |
| Zdroj: | ACS Combinatorial Science |
| ISSN: | 2156-8944 2156-8952 |
| DOI: | 10.1021/co500043q |
| Popis: | Methods capable of exhaustively screening for crystal polymorphism remain an elusive goal in solid-state chemistry. Particularly promising among the new generation of approaches is polymer-induced heteronucleation (PIHn), a tool utilizing hundreds of unique polymers for granting kinetic access to polymorphs. Here PIHn is redeployed in a high density format in which 288 distinct polymers, each acting as a heteronucleant, are arrayed on one substrate. This format allows determining the outcome of thousands of crystallizations in an automated fashion with only a few milligrams of sample. This technology enables the study of a broader range of targets, including preclinical candidates, facilitating determination of polymorphism propensity much earlier in the drug development process. Here the efficacy of this approach is demonstrated using four pharmaceutically relevant compounds: acetaminophen, tolfenamic acid, ROY, and curcumin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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