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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F17%3A43914512" target="_blank" >RIV/60461373:22310/17:43914512 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22340/17:43914512

Result on the web

<a href="http://dx.doi.org/10.3390/cryst7010013" target="_blank" >http://dx.doi.org/10.3390/cryst7010013</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cryst7010013" target="_blank" >10.3390/cryst7010013</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10401 - Organic chemistry

Project

<a href="/en/project/GA16-10035S" target="_blank" >GA16-10035S: Preparation of pharmaceutical co-crystals and their structural characterization by combination of electron single-crystal and x-ray powder diffraction</a><br>

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

CRYSTALS

ISSN

2073-4352

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

1

Country of publishing house

CH - SWITZERLAND

Number of pages

16

Pages from-to

"JANUARY 2017"

UT code for WoS article

000395436400012

EID of the result in the Scopus database

2-s2.0-850104172468