Publication detail

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

MUSELÍK, J. URBANOVÁ, M. BARTONÍČKOVÁ, E. PALOVČÍK, J. VETCHÝ, D. CZERNEK, J. JANIŠOVÁ, L. VELYCHKIVSKA, N. FRANC, A. BRUS, J.

Original Title

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

Type

journal article in Scopus

Language

English

Original Abstract

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.

Keywords

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

Authors

MUSELÍK, J.; URBANOVÁ, M.; BARTONÍČKOVÁ, E.; PALOVČÍK, J.; VETCHÝ, D.; CZERNEK, J.; JANIŠOVÁ, L.; VELYCHKIVSKA, N.; FRANC, A.; BRUS, J.

Released

30. 8. 2021

Publisher

MDPI

Location

Basel, Switzerland

ISBN

1999-4923

Periodical

Pharmaceutics

Year of study

13

Number

9

State

Swiss Confederation

Pages from

1

Pages to

19

Pages count

19

URL

https://www.mdpi.com/1999-4923/13/9/1364

Full text in the Digital Library

http://hdl.handle.net/11012/201638

BibTex

@article{BUT172524,
  author="Jan {Muselík} and Martina {Urbanová} and Eva {Bartoníčková} and Jakub {Palovčík} and David {Vetchý} and Jiří {Czernek} and Larisa {Janišová} and Nadiia {Velychkivska} and Aleš {Franc} and Jiří {Brus}",
  title="Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution",
  journal="Pharmaceutics",
  year="2021",
  volume="13",
  number="9",
  pages="1--19",
  doi="10.3390/pharmaceutics13091364",
  issn="1999-4923",
  url="https://www.mdpi.com/1999-4923/13/9/1364"
}