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Article

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

1
Department of Pharmaceutical Technology, Faculty of Pharmacy, Masaryk University, Palackého třída 1946/1, 612 00 Brno, Czech Republic
2
Department of NMR Spectroscopy, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky sq. 2, 162 06 Prague 6, Czech Republic
3
Materials Research Centre, Faculty of Chemistry, Brno University of Technology, Purkyňova 464/118, 612 00 Brno, Czech Republic
*
Authors to whom correspondence should be addressed.
Academic Editor: Romána Zelkó
Pharmaceutics 2021, 13(9), 1364; https://doi.org/10.3390/pharmaceutics13091364
Received: 16 July 2021 / Revised: 26 August 2021 / Accepted: 27 August 2021 / Published: 30 August 2021
(This article belongs to the Special Issue Advanced Pharmaceutical Research in the Czech Republic)
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. View Full-Text
Keywords: warfarin; solid-state NMR; polymorphism; stability; particle size; bioavailability; generic substitution warfarin; solid-state NMR; polymorphism; stability; particle size; bioavailability; generic substitution
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MDPI and ACS Style

Muselík, J.; Urbanova, M.; Bartoníčková, E.; Palovčík, J.; Vetchý, D.; Czernek, J.; Janisova, L.; Velychkivska, N.; Franc, A.; Brus, J. Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution. Pharmaceutics 2021, 13, 1364. https://doi.org/10.3390/pharmaceutics13091364

AMA Style

Muselík J, Urbanova M, Bartoníčková E, Palovčík J, Vetchý D, Czernek J, Janisova L, Velychkivska N, Franc A, Brus J. Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution. Pharmaceutics. 2021; 13(9):1364. https://doi.org/10.3390/pharmaceutics13091364

Chicago/Turabian Style

Muselík, Jan, Martina Urbanova, Eva Bartoníčková, Jakub Palovčík, David Vetchý, Jiří Czernek, Larisa Janisova, Nadiia Velychkivska, Aleš Franc, and Jiří Brus. 2021. "Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution" Pharmaceutics 13, no. 9: 1364. https://doi.org/10.3390/pharmaceutics13091364

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