Warfarin sodium (WS) is anticoagulant drug that exists as racemic mixture of two optically active enantiomers, R and S. S-WS is 3-5 times more potent pharmacologically than R-WS. The chemical stability of R and S WS in the amorphous and crystalline forms is unknown which might cause a change in therapeutic outcome of such low therapeutic index drug. Therefore, the objective of this work is to evaluate the stability of WS under accelerated stability conditions using X-ray diffractometer as analytical technique. Eight WS products (A, B,C, D, E, F, G and H) were obtained from the market and stored in 60°C and 40° C/75% RH up to 3 months. The samples were tested on day 0, 7, 14, 28, 56 and 84 for any change of crystallinity using X-ray Diffractometer Bruker D8 Advance. Diffractograms were collected over 2Θ range of 5–30○ with an increment of 0.05○ at 6 secs per step. Diffractograms showed all products initially to have warfarin in crystalline state , where a distinctive peak at 8.2° 2Θ was used to identify warfarin crystallinity. At 60° C , all products (A to H) showed good stability up to 3 months with no conversion from crystalline to amorphous. At 40° C/75% RH, products (A, B, C , D , E and F) showed good stability with no change in intensity of peak at 8.2° 2Θ ,while products G and H showed complete conversion of WS from crystalline to amorphous after 14 days and 56 days, respectively. This study provides important information regarding warfarin’s physical and chemical stability using X-ray diffraction as an efficient analytical technique. The conversion of WS from crystalline to amorphous of some products might have the potential to affect the safety and efficacy of warfarin which could be a potential public health issue.

Evaluation of the stability of warfarin sodium crystallinity using X-ray diffractometer

2019 Spring National Meeting

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