New Applications of Electron Microscopy in Pharmaceuticals: Crystallinity Assessment and Polymorph Determination

Recently, transmission electron microscopy has been used in crystallinity assessments and unit cell parameter/polymorph determinations in solid drug substances [1,2]. Lumaxis™ (roxifiban) is a glycoprotein nb/ffla (GPHb/HIa) antagonist discovered recently at The DuPont Pharmaceuticals Company [3] currently undergoing clinical evaluation for the treatment of thrombotic disorders. Lumaxis™ is converted in vivo to a zwitterionic active metabolite, XV459. As reported here, we have assessed by electron microscopy and x-ray diffraction the crystallinity of XP280, the benzenesulfonate salt of XV459, and determined the unit cell parameters of SC877, the methanesulfonate salt of the methyl ester of XV459.Crystallinity assessment. Partial or complete transformation of crystalline phases into amorphous phases can occur during production processes that may ultimately affect the activity associated with various batches of a drug [4, 5]. Whether desired or not, the amorphous content of any drug substance is thus an important issue for the pharmaceutical industry.