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

Published online by Cambridge University Press:  23 July 2013

N. Masciocchi ,
A. Aulisio ,
G. Bertolini ,
M. Sada ,
F. Garis  and
L. Malpezzi
N. Masciocchi*
Affiliation:
Dipartimento di Scienza e Alta Tecnologia, Università dell'Insubria, via Valleggio 11, 22100 Como, Italy
A. Aulisio
Affiliation:
Dipartimento di Scienza e Alta Tecnologia, Università dell'Insubria, via Valleggio 11, 22100 Como, Italy
G. Bertolini
Affiliation:
Labochim spa, Via B. Cellini, 20, 20090, Segrate, Italy
M. Sada
Affiliation:
Labochim spa, Via B. Cellini, 20, 20090, Segrate, Italy
F. Garis
Affiliation:
Labochim spa, Via B. Cellini, 20, 20090, Segrate, Italy
L. Malpezzi
Affiliation:
Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, via Mancinelli 7, 20131 Milano, Italy
*
a) Author to whom correspondence should be addressed. Electronic mail: [email protected]
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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.

Keywords

ivabradine hydrochloridedrugpolymorphic formssolvatesXRPD
Type
Technical Articles
Information
Powder Diffraction , Volume 28 , Issue 3 , September 2013 , pp. 200 - 206
Copyright
Copyright © International Centre for Diffraction Data 2013 

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