Background Manipulation of drug formulations to achieve an appropriate dose is often necessary in the paediatric ward (e.g crushing and dispersion of tablets, followed by extraction of a fraction). However, such manipulation has previously been shown to result in inaccurate dosing for some tablet formulations of the poorly soluble anticoagulant aspirin. Using the same manipulation procedure, a dispersible tablet formulation of aspirin yielded 99% of the intended dose while a chewable tablet yielded only 9%.¹ Warfarin is another anticoagulant used in paediatric care. Despite having good solubility, ensuring a reliable dose of this substance is important, considering the narrow therapeutic index of the drug.

Purpose To investigate the dose accuracy and dose precision attained after manipulation of two different warfarin tablets, using validated ultra high-performance liquid chromatography (UHPLC-analysis).

Material and methods Warfarin tablets: Marevan (2.5 mg; Takeda AS, Norway) and Warfarin Orion (2.5 mg; Orion Pharma, Finland). Instrument: UHPLC-system from Shimadzu Corp (Nexera, with Prominence DAD-detector). Analytical column: Inertsil 2 µm C8–3, 2.1 × 100 mm, (GL Sciences Inc., Tokyo, Japan). The analytical method was validated for linearity, precision and specificity. Dosing accuracy study: six tablets from each of the two formulations were individually dissolved in 10 ml water. After 8 min, a sample (1 ml) was withdrawn. Dosing accuracy and precision was recorded and compared between formulations.

Results For Warfarin Orion (2.5 mg) 96.5% (SD 4.8; range 89.8%–101.4%) of the intended dose was found. For Marevan (2.5 mg) 101.4% (SD 4.2; range 96.3%–107.2%) of the intended dose was found.

Conclusion Using a validated UHPLC-method, the dosing accuracy upon dispersion and dose extraction from two warfarin tablets (Marevan and Warfarin Orion) was found to be both accurate and precise – unlike that which had previously been published for different aspirin tablets. These results underline the importance of considering both formulation and drug characteristics when manipulating tablets.

References and/or acknowledgements 1. Notaker N, Brustugun J, Tho I, Bjerknes K. Manipulation and formulation – the tale of two aspirin tablets. Poster abstract. EAHP 2016.

No conflict of interest.