Structural Changes of Sodium Warfarin in Tablets Affecting the
Dissolution Profiles and Potential Safety of Generic
Substitution

J 2021

Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution

MUSELÍK, Jan, M. URBANOVA, E. BARTONICKOVA, J. PALOVCIK, David VETCHÝ et. al.

Základní údaje

Originální název

Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution

Autoři

MUSELÍK, Jan (203 Česká republika, domácí), M. URBANOVA, E. BARTONICKOVA, J. PALOVCIK, David VETCHÝ (203 Česká republika, domácí), J. CZERNEK, L. JANISOVA, N. VELYCHKIVSKA, Aleš FRANC (203 Česká republika, garant, domácí) a J. BRUS

Vydání

Pharmaceutics, BASEL, MDPI, 2021, 1999-4923

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.525

Kód RIV

RIV/00216224:14160/21:00122723

Organizační jednotka

Farmaceutická fakulta

DOI

http://dx.doi.org/10.3390/pharmaceutics13091364

UT WoS

000701490900001

Klíčová slova anglicky

warfarin; solid-state NMR; polymorphism; stability; particle size; bioavailability; generic substitution

Štítky

rivok, ÚFT

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 3. 2022 16:12, JUDr. Sabina Krejčiříková

Anotace

V originále

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.

Návaznosti

MUNI/A/1574/2020, interní kód MU

Název: Pokročilé technologie pro přípravu a hodnocení částicových systémů

Investor: Masarykova univerzita, Pokročilé technologie pro přípravu a hodnocení částicových systémů

Citovat

MUSELÍK, Jan, M. URBANOVA, E. BARTONICKOVA, J. PALOVCIK, David VETCHÝ, J. CZERNEK, L. JANISOVA, N. VELYCHKIVSKA, Aleš FRANC a J. BRUS. Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution. Pharmaceutics. BASEL: MDPI, 2021, roč. 13, č. 9, s. 1-19. ISSN 1999-4923. Dostupné z: https://dx.doi.org/10.3390/pharmaceutics13091364.

@article{1800801,
   author = {Muselík, Jan and Urbanova, M. and Bartonickova, E. and Palovcik, J. and Vetchý, David and Czernek, J. and Janisova, L. and Velychkivska, N. and Franc, Aleš and Brus, J.},
   article_location = {BASEL},
   article_number = {9},
   doi = {http://dx.doi.org/10.3390/pharmaceutics13091364},
   keywords = {warfarin; solid-state NMR; polymorphism; stability; particle size; bioavailability; generic substitution},
   language = {eng},
   issn = {1999-4923},
   journal = {Pharmaceutics},
   title = {Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution},
   url = {https://www.mdpi.com/1999-4923/13/9/1364/htm},
   volume = {13},
   year = {2021}
}

TY  - JOUR
ID  - 1800801
AU  - Muselík, Jan - Urbanova, M. - Bartonickova, E. - Palovcik, J. - Vetchý, David - Czernek, J. - Janisova, L. - Velychkivska, N. - Franc, Aleš - Brus, J.
PY  - 2021
TI  - Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution
JF  - Pharmaceutics
VL  - 13
IS  - 9
SP  - 1-19
EP  - 1-19
PB  - MDPI
SN  - 19994923
KW  - warfarin
KW  - solid-state NMR
KW  - polymorphism
KW  - stability
KW  - particle size
KW  - bioavailability
KW  - generic substitution
UR  - https://www.mdpi.com/1999-4923/13/9/1364/htm
N2  - 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.
ER  -

MUSELÍK, Jan, M. URBANOVA, E. BARTONICKOVA, J. PALOVCIK, David VETCHÝ, J. CZERNEK, L. JANISOVA, N. VELYCHKIVSKA, Aleš FRANC a J. BRUS. Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution. \textit{Pharmaceutics}. BASEL: MDPI, 2021, roč.~13, č.~9, s.~1-19. ISSN~1999-4923. Dostupné z: https://dx.doi.org/10.3390/pharmaceutics13091364.

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