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Crystals 2017, 7(1), 13; doi:10.3390/cryst7010013

Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation

1
Department of Solid State Chemistry, University of Chemistry and Technology Prague, Technicka 5, 16628 Prague 6, Czech Republic
2
Zentiva, k.s., U kabelovny 130, 10237 Prague 10, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editor: Srinivasulu Aitipamula
Received: 11 November 2016 / Revised: 20 December 2016 / Accepted: 21 December 2016 / Published: 6 January 2017
(This article belongs to the Special Issue Novel Pharmaceutical Cocrystals and Their Applications)
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Abstract

The pharmaceutical salt ivabradine hydrochloride is indicated for the symptomatic treatment of chronic stable angina pectoris and chronic heart failure. It exhibits extensive polymorphism and co-crystallization, which could be a way to provide an alternative solid form. We conducted a co-crystal screen, from which two hits were identified: with (S)-mandelic and (R)-mandelic acid. Both structures were determined from single-crystal X-ray diffraction data as co-crystals. The co-crystals were further characterized by common solid-state techniques, such as X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), solid-state NMR, IR and Raman spectroscopy, and dynamic vapor sorption (DVS). The co-crystal with (S)-mandelic acid was selected for further development; its physical and chemical stability was compared with two different polymorphs of the hydrochloride salt. The co-crystal exhibited a similar stability with the polymorph used in the original drug product and was, therefore, selected for formulation into the drug product. During the pre-formulation experiments, the in situ formation of the co-crystal was achieved during the wet granulation process. The following formulation experiments showed no influence of in situ prepared co-crystal on the overall stability of the bulk, when compared with pre-prepared co-crystal formulation. View Full-Text
Keywords: co-crystals; crystal polymorphism; crystal structure; preformulation; X-ray powder diffractometry co-crystals; crystal polymorphism; crystal structure; preformulation; X-ray powder diffractometry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sládková, V.; Dammer, O.; Sedmak, G.; Skořepová, E.; Kratochvíl, B. Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation. Crystals 2017, 7, 13.

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