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

0495859 - ÚPT 2019 RIV NL eng J - Článek v odborném periodiku
Franc, A. - Muselík, J. - Zeman, J. - Lukášová, I. - Kurhajec, S. - Bartoníčková, E. - Galvánková, L. - Mika, Filip - Dominik, M. - Vetchý, D.
The effect of amorphous and crystal sodium warfarin and its content uniformity on bioequivalence of tablets.
European Journal of Pharmaceutical Sciences. Roč. 125, DEC (2018), s. 120-129. ISSN 0928-0987. E-ISSN 1879-0720
Grant CEP: GA MŠMT(CZ) LO1212; GA MŠMT ED0017/01/01
Institucionální podpora: RVO:68081731
Klíčová slova: warfarin sodium * polymorphism * dissolution * raman spectroscopy * x-ray * generic substitution
Obor OECD: Medical laboratory technology (including laboratory samples analysis
Impakt faktor: 3.532, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0288747