Abstract
The past decade has seen great strides in high-throughput experimentation in support of chemical process development in the pharmaceutical industry. This has been driven by the need for (1) comprehensive salt and polymorph screening, (2) rapid determination of methods for chemical, and (3) chiral purification. Using the concept behind combinatorial protein crystallization screening, several industry and academic groups have developed innovative platforms to perform such screening for small organic molecules. This chapter provides a historical overview of high-throughput phase screening as well as elucidates the fundamental scientific principles underlying such efforts. A detailed account of the most commonly used methods in crystal polymorph and salt screening as well as chemical and enantiomeric purification are provided along with case studies. In addition, a critical look at the future of high-throughput crystal polymorph and salt screening is presented, with an emphasis on evolving platforms and perspectives on manual approaches.
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