Disclosing the extensive crystal chemistry of Ivabradine hydrochloride, in its pure and solvated phases

Abstract

Powder diffraction data are presented for Ivabradine hydrochloride (pure and solvated forms), a drug marketed worldwide for symptomatic treatment of angina pectoris and inappropriate sinus tachycardia. [Ivrabradine: 3-[3-({[(7S)-3,4-dimethoxy bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one]. Many are the different (polymorphic or solvated) phases claimed in the scientific or forensic literature. We have here prepared monophasic samples of six different ivabradine hydrochloride species. Exposure to water vapours, at room temperature, of the anhydrous δ-d form generated pure powders of the tetrahydrate form (the β-form). Two different anhydrous forms (β-d and α) were prepared by gentle, or extensive, heating of the β and δ-d forms, respectively. Acetonitrile and acetone solvates (hereafter called δ1- and δ2-forms) were obtained by precipitation methods from concentrated solutions. Diffraction data were collected on laboratory equipment with Ni-filtered CuKα radiation; cell parameters and space groups were determined from ab initio indexing procedures using the SVD algorithm.