In-line monitoring of carvedilol crystallization using raman spectroscopy

Hajnalka Pataki, Imre Markovits, Balázs Vajna, Zsombor K. Nagy, György Marosi

Research output: Contribution to journalArticle

18 Citations (Scopus)


Real-time Raman spectroscopy was used to characterize the solvent-mediated polymorphic transition and cooling crystallization of carvedilol. Kinetically preferred Form II was transformed into thermodynamically stable Form I during solvent-mediated phase transitions in ethyl acetate. The transition rate into Form I increased with rising temperature; however, at 0 °C a solvate form (Form VII) appeared. In the case of cooling crystallizations, the Form II polymorph was formed at 16-9 wt % drug concentration, while metastable solvates crystallized from a diluted, 2.9 wt % solution. A new solvate form, Form V*, was identified during crystallization in ethyl acetate, which is presumably related to Form V (known as an ethyl methyl ketone solvate in the literature). This study demonstrates the advantages of in-line Raman spectroscopy for monitoring in situ pharmaceutical crystallization by detecting the intermediate polymorphic transitions, which is fundamental in the development and operation of industrial crystallization processes.

Original languageEnglish
Pages (from-to)5621-5628
Number of pages8
JournalCrystal Growth and Design
Issue number11
Publication statusPublished - Nov 7 2012

ASJC Scopus subject areas

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

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