Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation
AbstractThe 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
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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.
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(1):13.Chicago/Turabian Style
Sládková, Veronika; Dammer, Ondřej; Sedmak, Gregor; Skořepová, Eliška; Kratochvíl, Bohumil. 2017. "Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation." Crystals 7, no. 1: 13.
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