title: Solid-state carbon NMR characterization and investigation of intrinsic dissolution behavior of fluconazole polymorphs, anhydrate forms I and II.
abstract: Solid-state (13)C nuclear magnetic resonance ((13)C-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 (13)C-SSNMR. (1)H T(1) 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.
authors.affiliation: Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Wonkyung
authors.initials: W
authors.lastname: Cho
authors.forename: Junsung
authors.initials: J
authors.lastname: Park
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Cha
authors.forename: Young-Shin
authors.initials: YS
authors.lastname: Kang
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D003460:Crystallization; D015725:Fluconazole / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008968:Molecular Conformation; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole