Factor analysis in optimization of formulation of high content uniformity tablets containing low dose active substance

0480607 - ÚPT 2018 RIV NL eng J - Journal Article
Lukášová, I. - Muselík, J. - Franc, A. - Goněc, R. - Mika, Filip - Vetchý, D.
Factor analysis in optimization of formulation of high content uniformity tablets containing low dose active substance.
European Journal of Pharmaceutical Sciences. Roč. 109, NOV (2017), s. 541-547. ISSN 0928-0987. E-ISSN 1879-0720
R&D Projects: GA MŠMT(CZ) LO1212; GA MŠMT ED0017/01/01
Institutional support: RVO:68081731
Keywords : factor analysis * process optimization * sampling error * worst case
OECD category: Medical laboratory technology (including laboratory samples analysis
Impact factor: 3.466, year: 2017

Warfarin is intensively discussed drug with narrow therapeutic range. There have been cases of bleeding attributed to varying content or altered quality of the active substance. Factor analysis is useful for finding suitable technological parameters leading to high content uniformity of tablets containing low amount of active substance. The composition of tabletting blend and technological procedure were set with respect to factor analysis of previously published results. The correctness of set parameters was checked by manufacturing and evaluation of tablets containing 1-10mg of warfarin sodium. The robustness of suggested technology was checked by using worst case scenario and statistical evaluation of European Pharmacopoeia (EP) content uniformity limits with respect to Bergum division and process capability index (Cpk). To evaluate the quality of active substance and tablets, dissolution method was developed (water, EP apparatus II, 25rpm), allowing for statistical comparison of dissolution profiles. Obtained results prove the suitability of factor analysis to optimize the composition with respect to batches manufactured previously and thus the use of metaanalysis under industrial conditions is feasible.
Permanent Link: http://hdl.handle.net/11104/0276351