Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

作     者：U. Sailaja M. Shahin Thayyil N.S. Krishna Kumar G. Govindaraj 

作者机构：Department of Physics M.E.S Keveeyam College. Valanchery 676552 Malappuram Kerala India Department of Physics University of Calicut 673635 Kerala. India Department of Physics School of Physical Chemical and Applied Sciences Pondicherry University Puducherry 605014 India 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2016年第6卷第3期

页      面：165-170页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100704[医学-药物分析学] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 0702[理学-物理学] 10[医学] 

基　　金：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) 

主　　题：Amorphous fenofibrate Bioavailability Broadband dielectric spectroscopy Glass transition Molecular dynamics 

摘      要：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 per- formed 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.