Open AccessTowards Exhaustive and Automated High-Throughput Screening for Crystalline Polymorphs
Author(s) -
Laura Y. Pfund,
Adam J. Matzger
Publication year - 2014
Publication title -
acs combinatorial science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.928
H-Index - 81
eISSN - 2156-8952
pISSN - 2156-8944
DOI - 10.1021/co500043q
Subject(s) - chemistry , polymer , polymorphism (computer science) , combinatorial chemistry , high throughput screening , solid state , nanotechnology , organic chemistry , biochemistry , allele , materials science , gene
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.