RESUMO
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 48â¯h. The MIC values obtained for the antibiotics used were within a permissible range for comparison.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Impressão Tridimensional , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Tinta , Viabilidade Microbiana , ImpressãoRESUMO
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 30â¯days. Therapeutic warfarin doses (1.25 and 2.5â¯mg) were successfully printed onto the film substrates. Excellent linearity was observed between the theoretical and measured dose by changing the warfarin feed concentration (R2â¯=â¯0.9999) and length of the print objective, i.e. the Y-value, (R2â¯=â¯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.
Assuntos
Anticoagulantes/química , Impressão , Varfarina/química , Composição de Medicamentos/métodos , Medicina de PrecisãoRESUMO
The aim of this work was to compare and contrast the mechanical properties and physical stabilities of oral films prepared with either thermal ink-jet printing (TIJP) or solvent casting (SC). Clonidine hydrochloride was selected as a model drug because of its low therapeutic dose and films were prepared using cellulose polymers. Mechanical testing showed that the printed films had Young's moduli and tensile strength values similar to the free film, while casted films were significantly more brittle. The drug also appeared to crystallize out of casted films during stress testing whereas printed films remained unchanged. The dissolution behavior of printed and cast films were similar, because of the rapid disintegration of the polymer. The conclusion is that printing resulted in a better film than casting because the drug resided on the film, rather than in the film where it could exert a plasticizing effect.