Diversity in Itraconazole Cocrystals with Aliphatic Dicarboxylic Acids of Varying Chain Length

Anna Shevchenko*, Inna Miroshnyk, Lars-Olof Pietilä, Jorma Haarala, Jukka Salmia, Kai Sinervo, Sabiruddin Mirza, Bert van Veen, Erkki Kolehmainen, Nonappa Nonappa, Jouko Yliruusi

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

29 Citations (Scopus)

Abstract

The cocrystal formation potential of itraconazole, a potent antifungal drug, with C2-C10 aliphatic dicarboxylic acids has been investigated. Using two experimental screening techniques (solvent-assisted grinding and evaporation-based crystallization), the cocrystals of itraconazole with C2-C7 dicarboxylic acids have been successfully synthesized and characterized by powder X-ray diffraction, solid state nuclear magnetic resonance, Raman spectroscopy, and thermal analysis. The characterized multicomponent compounds include anhydrous cocrystals (malonic, succinic, glutaric, and pimelic acids), a cocrystal hydrate (adipic acid), and cocrystal solvates with acetone and tetrahydrofuran (oxalic acid). This study is the first to demonstrate the diversity in itraconazole cocrystals with a range of aliphatic dicarboxylic acids of variable carbon chain lengths.

Original languageEnglish
Pages (from-to)4877-4884
Number of pages8
JournalCrystal Growth and Design
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 2013
MoE publication typeA1 Journal article-refereed

Keywords

  • SOLID-STATE PROPERTIES
  • PHARMACEUTICAL COCRYSTALS
  • CO-CRYSTAL
  • SOLUBILITY ADVANTAGE
  • CARBOXYLIC-ACIDS
  • HYDROGEN-BONDS
  • DRUG
  • DISSOLUTION
  • IMPROVE
  • PHARMACOKINETICS

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