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Towards exhaustive and automated high-throughput screening for crystalline polymorphs.

Pfund LY, Matzger AJ - ACS Comb Sci (2014)

Bottom Line: 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.Here the efficacy of this approach is demonstrated using four pharmaceutically relevant compounds: acetaminophen, tolfenamic acid, ROY, and curcumin.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and the Macromolecular Science and Engineering Program, University of Michigan , Ann Arbor, Michigan 48109, United States.

ABSTRACT
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.

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Ramanspectra of curcumin forms I, II, and III, obtained directlyfrom crystals on a μPIHn plate.
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fig6: Ramanspectra of curcumin forms I, II, and III, obtained directlyfrom crystals on a μPIHn plate.

Mentions: Curcumin is the primary curcuminoid in thespice turmeric. Curcumin has been found to act as an anti-inflammatory,anticancer, and anti-HIV agent.25 Nangiaand co-workers discovered two new polymorphs of curcumin while attemptingto form cocrystals.22 All three polymorphsof curcumin were found in the present study (Figure 6). Form I and II formed on polymers within the polar nitrogenlibrary, whereas form III nucleated on polymers within the acidiclibrary (see Supporting Information).


Towards exhaustive and automated high-throughput screening for crystalline polymorphs.

Pfund LY, Matzger AJ - ACS Comb Sci (2014)

Ramanspectra of curcumin forms I, II, and III, obtained directlyfrom crystals on a μPIHn plate.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215906&req=5

fig6: Ramanspectra of curcumin forms I, II, and III, obtained directlyfrom crystals on a μPIHn plate.
Mentions: Curcumin is the primary curcuminoid in thespice turmeric. Curcumin has been found to act as an anti-inflammatory,anticancer, and anti-HIV agent.25 Nangiaand co-workers discovered two new polymorphs of curcumin while attemptingto form cocrystals.22 All three polymorphsof curcumin were found in the present study (Figure 6). Form I and II formed on polymers within the polar nitrogenlibrary, whereas form III nucleated on polymers within the acidiclibrary (see Supporting Information).

Bottom Line: 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.Here the efficacy of this approach is demonstrated using four pharmaceutically relevant compounds: acetaminophen, tolfenamic acid, ROY, and curcumin.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and the Macromolecular Science and Engineering Program, University of Michigan , Ann Arbor, Michigan 48109, United States.

ABSTRACT
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.

Show MeSH