Photochemical stability of warfarin potassium in powdered pharmaceutical tablets

Abstract

BACKGROUND: Warfarin potassium (Wf) commercial tablets originally formulated for adults are ground before administration to pediatric patients and elderly patients with dysphagia. OBJECTIVE: The present study investigated the effect of tablet grinding on the photostability of four types of commercial Wf tablets and predicted the photostability of the tablet powders by chemometric analysis. METHODS: The photodegradation of Wf content was evaluated by reversed-phase column high-performance liquid chromatography with ultraviolet (HPLC-UV). RESULTS: The bulk Wf powder was relatively photostable, whereas ground Wf tablets underwent substantial photodegradation. The photostability of the ground powders of a brand-name Wf commercial tablet and three generic Wf commercial tablets was quantitatively assessed and compared. In certain cases, the Wf in all the three ground generic tablets was less photostable than in the ground brand-name tablets. After 28 days of light irradiation, the Wf content decreased to 69.79% in the brand-name tablets, while it was 31.90% in some generic tablets. To clarify the factors influencing the relative photostability in various Wf formulations, we analyzed the intermolecular interactions between the active ingredient and the excipients by partial least-squares regression analysis based on photostability screening for each additive. CONCLUSION: The results suggested that the additives light anhydrous silicic acid and povidone adversely affect the stability of Wf tablets. In addition, the light stability of ground tablets was affected considerably by their formulation.