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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" }