Detail publikace

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.

Originální název

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

Typ

článek v časopise ve Scopus, Jsc

Jazyk

angličtina

Originální abstrakt

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.

Klíčová slova

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

Autoři

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

Vydáno

30. 8. 2021

Nakladatel

MDPI

Místo

Basel, Switzerland

ISSN

1999-4923

Periodikum

Pharmaceutics

Ročník

13

Číslo

9

Stát

Švýcarská konfederace

Strany od

1

Strany do

19

Strany počet

19

URL

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

Plný text v Digitální knihovně

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"
}