Warfarin is a widely used anticoagulant that is critical in reducing patient morbidity and mortality associated with thromboembolic disorders. However, its narrow therapeutic index and large inter-individual variability can lead to complex dosage regimes. Formulating warfarin as an orodispersible film (ODF) using thermal ink-jet (TIJ) printing could enable personalisation of therapy to simplify administration. Commercial TIJ printers are currently unsuitable for printing the milligram dosages, typically required for warfarin therapy. As such, this study aimed to modify a commercial TIJ printing system to formulate personalised warfarin ODFs containing therapeutic dosages. A TIJ printer was modified successfully with the printer functionality intact; the substrate (paper) rolling mechanism of the printer was replaced by printing onto a stationary stage. Free film substrates were composed of hydroxypropyl methylcellulose (20%w/w) and glycerol (3%w/w). The resulting ODFs were characterised for morphology, disintegration, solid-state properties and drug content. Printed film stability was assessed at 40 °C/75% relative humidity for 30 days. Therapeutic warfarin doses (1.25 and 2.5 mg) were successfully printed onto the film substrates. Excellent linearity was observed between the theoretical and measured dose by changing the warfarin feed concentration (R = 0.9999) and length of the print objective, i.e. the Y-value, (R = 0.9998). Rapid disintegration of the ODFs was achieved. As such, this study successfully formulated personalised warfarin ODFs using a modified TIJ printer, widening the range of applications for TIJ printing to formulate narrow therapeutic index drugs.
An inexpensive method for determining minimum inhibitory concentrations (MIC) using ink-jet printing to deposit drug solutions and bacterial suspensions onto agar was developed. Substrate concentrations were varied using a "Y-value", whereby a series of rectangles with the same width and colour but different heights were printed within a fixed unit area. Prior to MIC determination, the printer cartridges used were calibrated using Fast Green dye. The impact of thermal ink-jet printing on bacterial viability was assessed by colony counting and found not to be deleterious. MIC determinations were conducted by printing varying concentrations of the antibiotics onto agar-coated glass slides then printing a thin even film of a known bacterial density of Lactobacillus acidophilus. Broth microdilution was performed simultaneously to validate the results. Slides and well plates were then incubated anaerobically for 48 hours. The MIC values obtained for the antibiotics used were within a permissible range for comparison.
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