Alomari, MHA; (2016) Application of thermal inkjet systems: Personalised dosing of medicines. Doctoral thesis , UCL (University College London).

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Abstract

Anticoagulation and hypothyroidism are common conditions which require precise yet highly variable range of doses that is not sufficiently met by traditional methods of oral dosing. The challenge of producing a therapeutic range of doses for the smaller dose range of levothyroxine for hypothyroidism and larger dose range of warfarin for anticoagulation using a re-engineered inkjet system is tackled. A novel re-engineered off-the-shelf system is used to produce accurate, precise and more flexible doses. Water seems to be an ideal solvent for the system; the system can accommodate ethanol content for up to 50% v/v. Distances of 2-3 mm from the stage to printhead are ideal for printing. The system is used to dispense actives having shown no significant difference between cartridges and printers and robustness when subjected to demanding physical conditions of autoclaving. Dosing models, methods through which variable doses can be produced with the system, are explored. Shade printing, a technique available in all inkjet systems, is characterised and found to produce non-linear dose control and relatively smaller maximum dose capacity. A novel dose model is introduced, named height-value printing, which utilised the modified system capacity and is shown to produce doses exceeding the maximum currently reported by inkjet systems. Optical dose confirmation by means of scanner is introduced for the produced doses, showing correlation with the quantitation of doses by HPLC (R2 of 0.9) for levothyroxine and warfarin. Sticking of the substrate and lower and higher dosing limitations of the technique are explored. The taste of levothyroxine films is investigated in rodent models and shown to be well accepted when compared to water or simulated pH-buffered saliva. Stability of the jetting solution and produced films are investigated and found to be lower for films. A further application of simultaneous and independent dispensing of pharmaceuticals, levothyroxine and liothyronine is investigated. The work unlocks the potential of inkjet systems to address drug personalisation challenges.

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