Polymorphism Screening Of Fenofibrate Usinga Polymer-induced Process

Polymorphic forms of a drug substance have different chemical and physical properties,including melting point,chemical reactivity,apparent solubility,dissolution rate,optical and mechanical properties,vapor pressure,and density.These properties have a direct effect on the ability to process and/or manufacture the drug substance and the drug product,as well as on drug product stability,dissolution,and bioavailability.So it is important to control the polymorphic forms.Polymorphic transformation can be induced by several methods,such as solvent evaporation,crystal magma,mechanical mill,melt cooling and etc.This project was focusing on polymorphism screening of Fenofibrate.Firstly,polymer materials such as Polyvinylpyrrolidone(PVP)were used as crystallization additives in polymorphism screening.The powder X-ray Diffraction(PXRD),Differential Scanning Calorimetry(DSC),Fourier Transform Infrared Spectroscopy(FTIR)were used to differentiate the obtained form and other known forms.The obtained form was a new form and named Form IV.Then stability and solubility of fenofibrate Form IV was studied.Humidity-stability test,light-stability and milling test showed the Form IV was stable.Solubility test showed this new form was more soluble than Form I in 0.5% tween-80 solution.Finally,molecular structure simulation technique(Material studio)was used to simulate internal structure of fenofibrate Form IV.The transition mechanism of fenofibrate polymorphism was speculated.The results of the project have an important guiding significance for controlling the existing medicinal preponderant drug crystal and looking for new drug polymorphs.