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

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ID: 66481
2017
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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.
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Authors Sládková, Veronika;Dammer, Ondřej;Sedmak, Gregor;Skořepová, Eliška;Kratochvíl, Bohumil;
Journal crystals
Year 2017
DOI
DOI not found
URL
http://www.mdpi.com/2073-4352/7/1/13
Keywords
chemistry Organic Chemistry Pharmacy and materia medica Therapeutics. Pharmacology Medicine arctic medicine. tropical medicine crystallography miscellaneous systems and treatments crystal structure preformulation crystal polymorphism

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