Research on Polymorphs of Edaravone / 医药导报

ABSTRACT

Objective To study polymorphism of the free radical scavenger edaravone and to find the one which has good advantages to the clinical medication. Methods Preparation of four forms of edaravone through kinds of physical or chemical methods. These polymorphs were characterized by single crystal X-ray diffraction method (SXRD), powder X-ray diffraction method (PXRD), differential scanning calorimetry method (DSC), infrared spectrum method (IR) and melting point method (MP);a variety of influence factors experiment were used to research the stability of polymorphs. Solid edaravone in different forms were orally administered to SD rats respectively, the plasma concentration of the drug was determined by HPLC, and the pharmacokinetic characteristic of different forms was compared according to the HPLC results. Results Four forms(form A, form B, form C, form D) and the preparation of pure crystal forms were obtained by crystal screening technology. These polymorphs were identified by PXRD, DSC and IR. The edaravone polymorphs have an influence on the stability and pharmacokinetic. Conclusion Edaravone research provideds a variety of crystal material composition, preparation methods, stability, solubility and pharmacokinetic characteristic, and form A has been proved of good advantage one. This research provides data and technology support for choice of preponderant pharmaceutical polymorphs and drug quality standard improvement.