The determination of crystal structures of active pharmaceutical ingredients from X-ray powder diffraction data: a brief, practical introduction, with fexofenadine hydrochloride as example.

Abstract

This study describes the general method for the determination of the crystal structures of active pharmaceutical ingredients (API) from powder diffraction data and demonstrates its use to determine the hitherto unknown crystal structure of fexofenadine hydrochloride, a third-generation antihistamine drug. Fexofenadine hydrochloride was subjected to a series of crystallisation experiments using re-crystallisation from solvents, gas diffusion, layering with an antisolvent and gel crystallisation. Powder diffraction patterns of all samples were recorded and inspected for polymorphism and for crystallinity. All samples corresponded to the same polymorph. The crystal structure was determined from an X-ray powder diffraction pattern using a real-space method with subsequent Rietveld refinement. The structure exhibits a two-dimensional hydrogen bond network. Crystal structures of API can be determined from X-ray powder diffraction data with good reliability. Fexofenadine exhibits only one polymorphic form, which is stabilised in the crystal by strong hydrogen bonds of the type (+)N-H···Cl(-), O-H···Cl(-), and between COOH groups.