Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate

Abstract

Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL. Furthermore, such structural characterization can assist with the development of new pharmaceutical products containing HSCL and also be useful in the identification of counterfeit drugs.

Keywords: GIPAW calculations; ab initio calculations; clopidogrel hydrogensulfate; crystal structure; polymorphism; solid dosage forms; solid-state NMR.