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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/60461373:22340/17:43914512

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA16-10035S" target="_blank" >GA16-10035S: Příprava farmaceutických kokrystalů a určování jejich krystalové struktury kombinací monokrystalové elektronové a RTG práškové difrakce</a><br>

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

CRYSTALS

ISSN

2073-4352

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

"JANUARY 2017"

Kód UT WoS článku

000395436400012

EID výsledku v databázi Scopus

2-s2.0-850104172468