Solid-state carbon NMR characterization and investigation of intrinsic dissolution behavior of fluconazole polymorphs, anhydrate forms I and II

Hee Jun Park, Min Soo Kim, Jeong Soo Kim, Wonkyung Cho, Junsung Park, Kwang Ho Cha, Young Shin Kang, Sung Joo Hwang

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Abstract

Solid-state 13C nuclear magnetic resonance (13C- SSNMR) revealed significant differences in the chemical shift of specific carbon atoms between two fluconazole polymorphs, reflecting a change in molecular conformation. A single resonance signal without splitting was observed in the spectrum of anhydrate form II, while the spectrum of anhydrate form I showed signals with splitting, indicating the presence of two dissimilar molecular conformations in the unit cell of anhydrate form I. The Fourier transform infrared (FT-IR) and Raman spectra associated with the triazole group, the 2,4-difluorobenzyl group, and the propane backbone provided also evidence of structural differences between forms I and II accompanying with 13C-SSNMR. 1H T1 relaxation times, measured using saturation recovery experiments, showed that the metastable anhydrate form II was more mobile than the stable form I. The solubility and intrinsic dissolution tests showed that the anhydrate form II was more soluble and dissolved faster than the anhydrate form I.

Original languageEnglish
Pages (from-to)1243-1247
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume58
Issue number9
DOIs
Publication statusPublished - 2010 Sep 1

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All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

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