Publication detail

The effect of amorphous and crystal sodium warfarin and its content uniformity on bioequivalence of tablets

FRANC, A. MUSELÍK, J. ZEMAN, J. LUKÁŠOVÁ, I. KURHAJEC, S. BARTONÍČKOVÁ, E. GALVÁNKOVÁ, L. MIKA, F. MARTIN, D. VETCHÝ, D.

Original Title

The effect of amorphous and crystal sodium warfarin and its content uniformity on bioequivalence of tablets

Type

journal article in Web of Science

Language

English

Original Abstract

Warfarin is intensively discussed in terms of generic substitution due to particular cases of bleeding, which are attributable to fluctuations in API content or the substitution of crystalline (WSC) for amorphous (WSA) warfarin. The aim of this study was to assess to what extent the in vitro release was affected by the form of API depending on the composition and technology. Bioequivalent tablets containing 5 mg of WSA or WSC prepared by we granulation or direct compression were used. Furthermore, tablets of the same composition with WSC or WSA prepared by direct compression were evaluated. Raman spectroscopy was used to confirm the presence of WSA or WSC. The dissolution was more influenced by the technology than by the form of API but even tablets with dissimilar profiles were bioequivalent. This is probably due to the precipitation of WSA and WSC in the stomach on a poorly soluble acidic form, which subsequently dissolves in the neutral environment of the small intestine. Recrystallization was demonstrated in the in vitro assay a a pH of 1.2 and 4.5 using Raman spectroscopy and X-ray diffraction. In summary, the content uniformity appears to be the main factor affecting the safety of the treatment

Keywords

Warfarin sodium; Polymorphism; Dissolution; Raman spectroscopy; X-ray; Generic substitution

Authors

FRANC, A.; MUSELÍK, J.; ZEMAN, J.; LUKÁŠOVÁ, I.; KURHAJEC, S.; BARTONÍČKOVÁ, E.; GALVÁNKOVÁ, L.; MIKA, F.; MARTIN, D.; VETCHÝ, D.

Released

1. 12. 2018

Publisher

ELSEVIER SCIENCE BV,

Location

AMSTERDAM, NETHERLANDS

ISBN

0928-0987

Periodical

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Number

125

State

Kingdom of the Netherlands

Pages from

120

Pages to

129

Pages count

10

URL

http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=1&SID=E1ef4BtSpJKfeCobRUR&page=1&doc=1

BibTex

@article{BUT151263,
  author="Aleš {Franc} and Jan {Muselík} and Jiří {Zeman} and Ivana {Lukášová} and Slavomír {Kurhajec} and Eva {Bartoníčková} and Lucie {Dlabajová} and Filip {Mika} and Dominik {Martin} and David {Vetchý}",
  title="The effect of amorphous and crystal sodium warfarin and its content uniformity on bioequivalence of tablets",
  journal="EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES",
  year="2018",
  number="125",
  pages="120--129",
  doi="10.1016/j.ejps.2018.09.022",
  issn="0928-0987",
  url="http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=1&SID=E1ef4BtSpJKfeCobRUR&page=1&doc=1"
}