Structural changes of sodium warfarin in tablets affecting the dissolution profiles and potential safety of generic substitution

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F21%3A00545620" target="_blank" >RIV/61389013:_____/21:00545620 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216305:26310/21:PU141616 RIV/00216224:14160/21:00122723

Výsledek na webu

<a href="https://www.mdpi.com/1999-4923/13/9/1364" target="_blank" >https://www.mdpi.com/1999-4923/13/9/1364</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/pharmaceutics13091364" target="_blank" >10.3390/pharmaceutics13091364</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structural changes of sodium warfarin in tablets affecting the dissolution profiles and potential safety of generic substitution

Popis výsledku v původním jazyce

At present, the risk of generic substitutions in warfarin tablets is still being discussed. The aim of this study was to assess whether API interactions with commonly used excipients may affect the safety of generic replacement of warfarin sodium tablets. These interactions were observed during an accelerated stability study, and the effect of the warfarin solid phase (crystalline/amorphous form) as well as the API particle size distribution was studied. Commercial tablets and prepared tablets containing crystalline warfarin or amorphous warfarin were used. In addition, binary mixtures of warfarin with various excipients were prepared. The structural changes before and after the stability study were monitored by dissolution test in different media, solid-state NMR spectroscopy and Raman microscopy. During the stability study, the conversion of the sodium in warfarin to its acid form was demonstrated by some excipients (e.g., calcium phosphate). This change in the solid phase of warfarin leads to significant changes in dissolution, especially with the different particle sizes of the APIs in the tablet. Thus, the choice of suitable excipients and particle sizes are critical factors influencing the safety of generic warfarin sodium tablets.

Název v anglickém jazyce

Structural changes of sodium warfarin in tablets affecting the dissolution profiles and potential safety of generic substitution

Popis výsledku anglicky

At present, the risk of generic substitutions in warfarin tablets is still being discussed. The aim of this study was to assess whether API interactions with commonly used excipients may affect the safety of generic replacement of warfarin sodium tablets. These interactions were observed during an accelerated stability study, and the effect of the warfarin solid phase (crystalline/amorphous form) as well as the API particle size distribution was studied. Commercial tablets and prepared tablets containing crystalline warfarin or amorphous warfarin were used. In addition, binary mixtures of warfarin with various excipients were prepared. The structural changes before and after the stability study were monitored by dissolution test in different media, solid-state NMR spectroscopy and Raman microscopy. During the stability study, the conversion of the sodium in warfarin to its acid form was demonstrated by some excipients (e.g., calcium phosphate). This change in the solid phase of warfarin leads to significant changes in dissolution, especially with the different particle sizes of the APIs in the tablet. Thus, the choice of suitable excipients and particle sizes are critical factors influencing the safety of generic warfarin sodium tablets.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/LTAUSA18011" target="_blank" >LTAUSA18011: Ab initio studie polymorfismu farmaceuticky aktivních látek podpořená přesnými NMR krystalografickými a kalorimetrickými experimenty</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Pharmaceutics

ISSN

1999-4923

e-ISSN

1999-4923

Svazek periodika

13

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

19

Strana od-do

1364

Kód UT WoS článku

000701490900001

EID výsledku v databázi Scopus

2-s2.0-85114262641