Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

U. Sailaja; M. Shahin Thayyil; N. S Krishna Kumar; G. Govindaraj

doi:10.1016/j.jpha.2014.09.003

Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

U. Sailaja, M. Shahin Thayyil, N. S Krishna Kumar, G. Govindaraj

Pharmaceutics

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry (DSC) shows that the aforesaid active pharmaceutical ingredient (API) is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were performed after its vitrification by fast cooling from a few degrees above the melting point (T_m=354.11 K) to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel–Fulcher–Tamman (VFT) equation. From VFT fit, glass transition temperature (T_g) was estimated as 250.56 K and fragility (m) was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch–Williams–Watts (KWW) fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai׳s coupling model, we identified the excess wing as true Johari–Goldstein (JG) process. Below the glass transition temperature one can clearly see a secondary relaxation (γ) with an activation energy of 32.67 kJ/mol.

Original language	English (US)
Pages (from-to)	165-170
Number of pages	6
Journal	Journal of Pharmaceutical Analysis
Volume	6
Issue number	3
DOIs	https://doi.org/10.1016/j.jpha.2014.09.003
State	Published - Jun 1 2016

Bibliographical note

Funding Information:
The authors gratefully acknowledge IIT Powai, Mumbai (India), CIL, NIPER, Mohali, (India) for providing experimental facilities. Sailaja acknowledges University Grants Commission (No. F.FIP/11th Plan/KLCA046TF, dated 12. May, 2009), Government of India for the award of a research fellowship under the Faculty Improvement Program (FIP).

Publisher Copyright:
© 2015 Xi'an Jiaotong University

Keywords

Amorphous fenofibrate
Bioavailability
Broadband dielectric spectroscopy
Glass transition
Molecular dynamics

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10.1016/j.jpha.2014.09.003

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title = "Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy",

abstract = "Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry (DSC) shows that the aforesaid active pharmaceutical ingredient (API) is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were performed after its vitrification by fast cooling from a few degrees above the melting point (Tm=354.11 K) to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel–Fulcher–Tamman (VFT) equation. From VFT fit, glass transition temperature (Tg) was estimated as 250.56 K and fragility (m) was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch–Williams–Watts (KWW) fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai׳s coupling model, we identified the excess wing as true Johari–Goldstein (JG) process. Below the glass transition temperature one can clearly see a secondary relaxation (γ) with an activation energy of 32.67 kJ/mol.",

keywords = "Amorphous fenofibrate, Bioavailability, Broadband dielectric spectroscopy, Glass transition, Molecular dynamics",

author = "U. Sailaja and Thayyil, {M. Shahin} and Kumar, {N. S Krishna} and G. Govindaraj",

note = "Funding Information: The authors gratefully acknowledge IIT Powai, Mumbai (India), CIL, NIPER, Mohali, (India) for providing experimental facilities. Sailaja acknowledges University Grants Commission (No. F.FIP/11th Plan/KLCA046TF, dated 12. May, 2009), Government of India for the award of a research fellowship under the Faculty Improvement Program (FIP). Publisher Copyright: {\textcopyright} 2015 Xi'an Jiaotong University",

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T1 - Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

AU - Sailaja, U.

AU - Thayyil, M. Shahin

AU - Kumar, N. S Krishna

AU - Govindaraj, G.

N1 - Funding Information: The authors gratefully acknowledge IIT Powai, Mumbai (India), CIL, NIPER, Mohali, (India) for providing experimental facilities. Sailaja acknowledges University Grants Commission (No. F.FIP/11th Plan/KLCA046TF, dated 12. May, 2009), Government of India for the award of a research fellowship under the Faculty Improvement Program (FIP). Publisher Copyright: © 2015 Xi'an Jiaotong University

PY - 2016/6/1

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N2 - Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry (DSC) shows that the aforesaid active pharmaceutical ingredient (API) is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were performed after its vitrification by fast cooling from a few degrees above the melting point (Tm=354.11 K) to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel–Fulcher–Tamman (VFT) equation. From VFT fit, glass transition temperature (Tg) was estimated as 250.56 K and fragility (m) was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch–Williams–Watts (KWW) fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai׳s coupling model, we identified the excess wing as true Johari–Goldstein (JG) process. Below the glass transition temperature one can clearly see a secondary relaxation (γ) with an activation energy of 32.67 kJ/mol.

AB - Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry (DSC) shows that the aforesaid active pharmaceutical ingredient (API) is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were performed after its vitrification by fast cooling from a few degrees above the melting point (Tm=354.11 K) to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel–Fulcher–Tamman (VFT) equation. From VFT fit, glass transition temperature (Tg) was estimated as 250.56 K and fragility (m) was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch–Williams–Watts (KWW) fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai׳s coupling model, we identified the excess wing as true Johari–Goldstein (JG) process. Below the glass transition temperature one can clearly see a secondary relaxation (γ) with an activation energy of 32.67 kJ/mol.

KW - Amorphous fenofibrate

KW - Bioavailability

KW - Broadband dielectric spectroscopy

KW - Glass transition

KW - Molecular dynamics

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DO - 10.1016/j.jpha.2014.09.003

M3 - Article

AN - SCOPUS:84919459965

SN - 2095-1779

VL - 6

SP - 165

EP - 170

JO - Journal of Pharmaceutical Analysis

JF - Journal of Pharmaceutical Analysis

IS - 3

ER -

Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

Abstract

Bibliographical note

Keywords

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