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

doi:10.1248/cpb.58.1243

Notes

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

Author information

Hee Jun Park
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University
Min-Soo Kim
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University
Jeong-Soo Kim
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University
Wonkyung Cho
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University
Junsung Park
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University
Kwang-Ho Cha
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University
Young-Shin Kang
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University
Sung-Joo Hwang
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University

Keywords: fluconazole, polymorph, solid-state nuclear magnetic resonance, solubility, intrinsic dissolution rate

JOURNAL FREE ACCESS

2010 Volume 58 Issue 9 Pages 1243-1247

DOI https://doi.org/10.1248/cpb.58.1243

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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.

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