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.

Basic information

Original name

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

Authors

MUSELÍK, Jan (203 Czech Republic, belonging to the institution), M. URBANOVA, E. BARTONICKOVA, J. PALOVCIK, David VETCHÝ (203 Czech Republic, belonging to the institution), J. CZERNEK, L. JANISOVA, N. VELYCHKIVSKA, Aleš FRANC (203 Czech Republic, guarantor, belonging to the institution) and J. BRUS

Edition

Pharmaceutics, BASEL, MDPI, 2021, 1999-4923

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.525

RIV identification code

RIV/00216224:14160/21:00122723

Organization unit

Faculty of Pharmacy

DOI

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

UT WoS

000701490900001

Keywords in English

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

Abstract

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.

Links

MUNI/A/1574/2020, interní kód MU

Name: Pokročilé technologie pro přípravu a hodnocení částicových systémů

Investor: Masaryk University

Citovat

MUSELÍK, Jan, M. URBANOVA, E. BARTONICKOVA, J. PALOVCIK, David VETCHÝ, J. CZERNEK, L. JANISOVA, N. VELYCHKIVSKA, Aleš FRANC and J. BRUS. Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution. Pharmaceutics. BASEL: MDPI, 2021, vol. 13, No 9, p. 1-19. ISSN 1999-4923. Available from: 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 and J. BRUS. Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution. \textit{Pharmaceutics}. BASEL: MDPI, 2021, vol.~13, No~9, p.~1-19. ISSN~1999-4923. Available from: https://dx.doi.org/10.3390/pharmaceutics13091364.

Detailed Information on Publication Record