Solid-State Carbon NMR Characterization and Investigation of Intrinsic Dissolution Behavior of Fluconazole Polymorphs, Anhydrate Forms I and II
Solid-State Carbon NMR Characterization and Investigation of Intrinsic Dissolution Behavior of Fluconazole Polymorphs, Anhydrate Forms I and II
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DOI：
10.1248/cpb.58.1243
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发表时间：
2010-09-01
影响因子：
1.7
通讯作者：
Hwang, Sung-Joo
中科院分区：
文献类型：
--
作者：
Park, Hee Jun;Kim, Min-Soo;Hwang, Sung-Joo
固态C-13核磁共振（C-13-SSNMR）揭示了显着的差异，在特定的碳原子的化学位移之间的两个氟康唑多晶型物，反映了分子构象的变化。在无水物形式II的光谱中观察到没有分裂的单个共振信号，而无水物形式I的光谱显示出具有分裂的信号，表明在无水物形式I的晶胞中存在两种不同的分子构象。与三唑基团、2，4-二氟苄基和丙烷主链相关的傅里叶变换红外（FT-IR）和拉曼光谱还提供了伴随C-13-SSNMR的形式I和II之间的结构差异的证据。使用饱和恢复实验测量的H-1 T-1弛豫时间表明，亚稳无水物形式II比稳定形式I更易移动的。溶解度和固有溶出试验表明，无水物形式II比无水物形式I更易溶解且溶解更快。
Solid-state C-13 nuclear magnetic resonance (C-13-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 C-13-SSNMR. H-1 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.