Microfluidic approach to cocrystal screening of pharmaceutical parent compounds

Sachit Goyal, Michael R. Thorson, Geoff G.Z. Zhang, Yuchuan Gong, Paul J.A. Kenis

Research output: Contribution to journalArticle

Abstract

We describe a microfluidic approach to screen for the formation of cocrystalline solid forms of pharmaceutical parent compounds (PCs). Saturated solutions of PCs and of cocrystal formers dissolved in a variety of solvents are precisely metered in arrays of 48 wells to enable the combinatorial mixing of all possible combinations. Key characteristics of the microfluidic approach, including small quantities (240 μg/48 conditions), the ability to generate and screen 48 unique conditions per chip, and the ability to identify solid forms on-chip via Raman spectroscopy, enable solid form screening very early in the drug development process. In contrast, current approaches require on the order of 240 mg for 48 conditions, thus delaying solid form screening to later stages of the drug development. Sequential screening experiments using caffeine as the model compound were conducted to validate the on-chip approach reported here. Preliminary screens were executed to identify conditions with the highest propensity for crystallization and to identify the cocrystal formers (CCFs) resulting in formation of cocrystals via on-chip Raman spectroscopy. Next, the identified, promising conditions were replicated to confirm reproducibility and consistency of the on-chip outcomes. Nine cocrystals of caffeine were identified in this way.

Original languageEnglish (US)
Pages (from-to)6023-6034
Number of pages12
JournalCrystal Growth and Design
Volume12
Issue number12
DOIs
StatePublished - Dec 5 2012

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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