Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study. / Heinz, Andrea; Gordon, Keith C; McGoverin, Cushla M; Rades, Thomas; Strachan, Clare J.

In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Vol. 71, No. 1, 2009, p. 100-8.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Heinz, A, Gordon, KC, McGoverin, CM, Rades, T & Strachan, CJ 2009, 'Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study', European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, vol. 71, no. 1, pp. 100-8. https://doi.org/10.1016/j.ejpb.2008.05.030

APA

Heinz, A., Gordon, K. C., McGoverin, C. M., Rades, T., & Strachan, C. J. (2009). Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 71(1), 100-8. https://doi.org/10.1016/j.ejpb.2008.05.030

Vancouver

Heinz A, Gordon KC, McGoverin CM, Rades T, Strachan CJ. Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2009;71(1):100-8. https://doi.org/10.1016/j.ejpb.2008.05.030

Author

Heinz, Andrea ; Gordon, Keith C ; McGoverin, Cushla M ; Rades, Thomas ; Strachan, Clare J. / Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study. In: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2009 ; Vol. 71, No. 1. pp. 100-8.

Bibtex

@article{4e42168c0ea04c00a26e61f0abda86bc,
title = "Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study",
abstract = "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.",
keywords = "Chemistry, Pharmaceutical, Crystallization, Fenofibrate, Hydrogen Bonding, Models, Molecular, Multivariate Analysis, Quantum Theory, Spectroscopy, Fourier Transform Infrared, Spectrum Analysis, Raman, Technology, Pharmaceutical, Vibration",
author = "Andrea Heinz and Gordon, {Keith C} and McGoverin, {Cushla M} and Thomas Rades and Strachan, {Clare J}",
year = "2009",
doi = "10.1016/j.ejpb.2008.05.030",
language = "English",
volume = "71",
pages = "100--8",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Understanding the solid-state forms of fenofibrate - a spectroscopic and computational study

AU - Heinz, Andrea

AU - Gordon, Keith C

AU - McGoverin, Cushla M

AU - Rades, Thomas

AU - Strachan, Clare J

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Chemistry, Pharmaceutical

KW - Crystallization

KW - Fenofibrate

KW - Hydrogen Bonding

KW - Models, Molecular

KW - Multivariate Analysis

KW - Quantum Theory

KW - Spectroscopy, Fourier Transform Infrared

KW - Spectrum Analysis, Raman

KW - Technology, Pharmaceutical

KW - Vibration

U2 - 10.1016/j.ejpb.2008.05.030

DO - 10.1016/j.ejpb.2008.05.030

M3 - Journal article

C2 - 18590814

VL - 71

SP - 100

EP - 108

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 1

ER -

ID: 40353146