کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2084511 1545391 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Understanding the solid-state forms of fenofibrate – A spectroscopic and computational study
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Understanding the solid-state forms of fenofibrate – A spectroscopic and computational study
چکیده انگلیسی

The aim of this study was to investigate the structure of different solid-state forms of fenofibrate, a drug that lacks strong intermolecular interactions such as hydrogen bonding. In addition to a structural analysis of crystalline and amorphous fenofibrate using infrared and Raman spectroscopy combined with density functional theory calculations [B3LYP 6-31G(d)], solid-state changes that occur upon recrystallization of amorphous fenofibrate were monitored and described using in situ Raman spectroscopy. A comparison of the calculated vibrational spectra of a fenofibrate monomer and two dimer structures with the experimental vibrational spectra of crystalline and amorphous fenofibrate revealed conformational differences in the orientation of the two benzyl rings in the fenofibrate molecule and structural differences between the different solid-state forms in aliphatic parts of the drug molecule. The spectroscopic analysis suggests that non-hydrogen-bonded drug molecules are likely to exhibit more random molecular orientations and conformations in the amorphous phase since the weak intermolecular interactions that occur between such molecules can easily be disrupted. In situ Raman spectroscopy and multivariate analysis revealed multiple solid-state forms of fenofibrate, including the metastable crystalline form II, which were structurally analyzed with reference to the quantum chemical calculations. Overall, the study showed that vibrational spectroscopy, multivariate analysis, and quantum chemical modeling are well suited to investigate and characterize the structure of drug substances that exhibit only small structural differences between different solid-state forms.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 71, Issue 1, January 2009, Pages 100–108
نویسندگان
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