Stability of warfarin sodium tablets repackaged in dose administration aids

Background: Dose administration aids (DAAs) are designed to assist patients to better manage their medicines. However, removal of a medicine from the original packaging invalidates the physicochemical stability guaranteed by the manufacturer. A few studies have investigated the stability of warfarin sodium; nevertheless there is no data available to suggest the stability of warfarin sodium in DAAs. Aim: To determine the stability of warfarin sodium tablets stored in DAAs and original packaging over a period of 8 weeks. Methods: Tablets were removed from primary packaging and repackaged into DAAs as whole tablets. DAAs and original packs were stored at controlled room temperature (25°C/60% relative humidity (RH)), accelerated (40°C/75% RH) and 'uncontrolled room temperature' (19-21°C and 38-50% RH) conditions for up to 8 weeks. The chemical stability was evaluated using a validated highperformance liquid chromotography method. Tablet hardness was determined using a texture analyser and dissolution profile was determined using a US Pharmacopeia apparatus 2. X-ray powder diffraction was used to investigate the crystalline structure of warfarin sodium. Results: There was no significant change in warfarin content at 8 weeks. Tablet hardness increased significantly when stored at accelerated and controlled room temperature conditions. Hardness of tablets stored in original packaging was comparable to that of DAAs at 8 weeks. The dissolution profile of tablets stored in original containers at accelerated conditions for 8 weeks was significantly different to that of baseline. Conclusions: Repackaging of warfarin sodium tablets into DAAs does not affect the chemical stability. However, tablets should be stored in a cool, dry place to minimise the effects on physical properties.