Multi-material hot-melt inkjet 3D printing: towards complex and personalised dosage form

Lion, Anna (2021) Multi-material hot-melt inkjet 3D printing: towards complex and personalised dosage form. PhD thesis, University of Nottingham.

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Three-dimensional printing includes a wide variety of manufacturing techniques, which are based on the digitally controlled deposition of materials (layer-by-layer) to create freeform 3D geometries. 3D printing with single-materials is a well-established technology that has found application across many different fields from engineering to medicine and pharmacy by enabling the production of complex and high quality prototypes and devices that were previously either difficult to manufacture expensive or time consuming.

The focus of this thesis is the design and development of a 3D system capable of fabricating, in a single additive process, multi-material solid dosage forms showing tailored release profiles. Hot-melt piezo-activated inkjet 3D printing was identified as an alternative to the traditional solvent based inkjet printing (IJP). Inks are kept liquid above their melting temperature eliminating the need of additional solvent and its consequent removal post processing step. This becomes of particular interest when considering those material, such as lipids which cannot be processed by traditional additive methods without the need of other excipients. Making thermal jetting for pharmaceutical application a great alternative 3DP method.

A commercially available printer was modified to include a dual reservoir unit capable of dispensing two different materials during the same additive process. A detailed description is presented of all the modifications and implementation introduced, including its main elements such as the choice of printer and printing head, the custom designed printing unit and supports, the temperature control and power supply system. In addition, the development of a complementary software update and slicing strategy is discussed. To complement the new set-up, a library of suitable material was established. Candidates were selected to comply with the limitations imposed by the printing technique (melting point below 90 °C and viscosity in the 8- 20 cP range) and on the base of their suitability for pharmaceutical use.

Specifically our attention focused on lipids, which present thermo-mechanical properties compatible with the range of interest. In addition, they are well known excipients used in traditional tableting techniques as enhancer in the delivery of poorly soluble drugs. Commonly used pharmaceutical lipids (Apifil CG, Candelilla, Compritol 888 ATO, Compritol HD5 ATO and Precirol ATO) and Fenofibrate (model drug) were used to prepare both drug-free and drug loaded inks with drug concentrations varying between 5% and 30% (w/w). Each ink formulation was thoroughly tested for printability to ensure compatibility with the method here reported.

Finally, the gathered knowledge was used to design and produce several proof-of-concept tailored release profile solid dosage forms. These included single and multi-material complex 3D patterns with defined localised drug loading where the drug-free ink is used as a release-regarding material to produce a series of tablets structures displaying immediate, extended, delayed and pulsatile drug release. This work adds significantly to the current landscape of 3D printing in that it illustrates the ability to design and build a multi-head hot-melt ink jet printer for the co-deposition of materials to form complex dosage forms with high spatial resolution. The potential of this approach is then illustrated with the manufacture of lipidic based complex geometry dosage forms able to demonstrate ‘programmable’ drug release patterns in in vitro studies.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Roberts, J. Clive
Wildman, D. Ricky
Morgan, R. Alexander
Keywords: three-dimensional printing, multi-material hot-melt inkjet 3D printing, dosage forms, pharmaceutical technology
Subjects: R Medicine > RS Pharmacy and materia medica
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 66762
Depositing User: Lion, Anna
Date Deposited: 19 Oct 2023 15:04
Last Modified: 19 Oct 2023 15:04

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