Application of two-level factorial design to investigate the effect of process parameters on the sonocrystallization of sulfathiazole

Peng Hsuan Kuo, Bo Cong Zhang, Chie Shaan Su, Jun Jen Liu, Ming Thau Sheu

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


In this study, cooling sonocrystallization was used to recrystallize an active pharmaceutical ingredient, sulfathiazole, using methanol as the solvent. The effects of three operating parameters-sonication intensity, sonication duration, and solution concentration-on the recrystallization were investigated by using a 2k factorial design. The solid-state properties of sulfathiazole, including the mean particle size, crystal habit, and polymorphic form, were analyzed. Analysis of variance showed that the effect of the sonication intensity, cross-interaction effect of sonication intensity/sonication duration, and cross-interaction effect of sonication intensity/solution concentration on the recrystallization were significant. The results obtained using the 2k factorial design indicated that a combination of high sonication intensity and long sonication duration is not favorable for sonocrystallization, especially at a high solution concentration. A comparison of the solid-state properties of the original and the recrystallized sulfathiazole revealed that the crystal habit of the recrystallized sulfathiazole was more regular and that its mean particle size could be reduced to approximately 10 μm. Furthermore, the analytical results obtained using the PXRD, DSC, and FTIR spectroscopy indicated that the polymorphic purity of sulfathiazole improved from the original Form III/IV mixture to Form III after sonocrystallization.

Original languageEnglish
Pages (from-to)8-14
Number of pages7
JournalJournal of Crystal Growth
Publication statusPublished - Aug 1 2017


  • A1. Polymorphism
  • A1. Recrystallization
  • A1: 2 Factorial design
  • B1. Organic compounds
  • B1. Pharmaceuticals

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Inorganic Chemistry
  • Materials Chemistry


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