Sailaja U, Thayyil M Shahin, Kumar N S Krishna, Govindaraj G
Department of Physics, M.E.S Keveeyam College, Valanchery, 676552 Malappuram, Kerala, India.
Department of Physics, University of Calicut, 673635 Kerala, India.
J Pharm Anal. 2016 Jun;6(3):165-170. doi: 10.1016/j.jpha.2014.09.003. Epub 2014 Sep 16.
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 (=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 () was estimated as 250.56 K and fragility () 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.
非诺贝特主要用于降低有心血管疾病风险患者的胆固醇水平。借助差示扫描量热法（DSC）进行的热转变研究表明，上述活性药物成分（API）是一种良好的玻璃态形成剂。基于我们的DSC研究，通过覆盖宽温度和频率范围的宽带介电谱（BDS）对该API的分子动力学进行了研究。将非晶态非诺贝特从熔点以上几度（=354.11 K）快速冷却至深玻璃态进行玻璃化后，进行了介电测量。样品在冷却过程中未显示出任何结晶趋势，并达到了玻璃态。结构弛豫的温度依赖性已通过单一的Vogel-Fulcher-Tamman（VFT）方程进行拟合。通过VFT拟合，玻璃化转变温度（）估计为250.56 K，脆性（）确定为94.02。这种药物被归类为易碎玻璃态形成剂。实验数据与α峰高频侧翼上的Kohlrausch-Williams-Watts（KWW）拟合的偏差表明非诺贝特中存在过量翼。基于Ngai的耦合模型，我们将过量翼识别为真正的Johari-Goldstein（JG）过程。在玻璃化转变温度以下，可以清楚地看到具有32.67 kJ/mol活化能的二级弛豫（γ）。
