Crystallization optimization of pharmaceutical solid forms with X-ray compatible microfluidic platforms

Elizabeth M. Horstman, Sachit Goyal, Ashtamurthy Pawate, Garam Lee, Geoff G.Z. Zhang, Yuchuan Gong, Paul J.A. Kenis

Research output: Contribution to journalArticlepeer-review


We describe a microfluidic approach to optimize crystallization of active pharmaceutical ingredients (APIs) and their solid forms (cocrystals) via crystal seeding. Subsequent on-chip X-ray diffraction is used to verify the crystal from. The microfluidic platform comprises an 8 × 9 well array that enables screening of seeding conditions (dilutions) by metering of API solution or API/cocrystal former solution and seed solution in ratios of 1:4 to 4:1, respectively, across each row. Slow solvent evaporation leads to seed growth and results in isolated diffraction quality crystals. To validate this microfluidic crystal seeding approach, three APIs (piroxicam, piracetam, and carbamazepine) and a cocrystal (carbamazepine/4-hydroxybenzoic acid) were used as model compounds. X-ray diffraction data was collected on-chip at room temperature to determine the crystal structure of the model compounds for comparison to published structural data. This on-chip seeding approach aided in crystallization of a desired solid form (e.g., a specific polymorph) over a mixture of solid forms. Easy handling, automated seeding and dilution, high throughput screening using small quantities of API (about 5 μg/well), and on-chip X-ray analysis of multiple crystals makes this platform attractive for solid form identification and characterization.

Original languageEnglish (US)
Pages (from-to)1201-1209
Number of pages9
JournalCrystal Growth and Design
Issue number3
StatePublished - Mar 4 2015

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics


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