LAUSR

Background: With the advent of personalised medicine, the need for flexible dosing is increasingly important. Conventional pharmaceutical manufacturing processes can be constrained in their ability to offer flexible dosing options to meet patient need. This is particularly important in specific populations, for example children, where available formulations are frequently not age-appropriate and need to be modified to achieve an intended dose. 3D-printing of solid dosage forms offers a disruptive technology which enables solid-dosage forms of medicines to be manufactured at flexible, precise doses meeting the needs of individual patients. This technology has relevance for manufacture of existing active pharmaceutical ingredients for a range of conditions including inflammatory diseases. Objectives: To develop 3D-printed oral solid dosage forms of medicines which are age-appropriate for children and young people. To determine the acceptability of 3D-printed medicines to children and young people by conducting interventional studies of tablet administration. Methods: Tablets containing a range of active pharmaceutical ingredients (API) were produced using two stages: (i) holt melt extrusion of a filament containing API and excipients; (ii) 3D printing of the filament using fused deposition modelling (FDM) to produce the desired shape in a layer-by-layer pattern. Acceptability of 3D-printed tablets to children and young people (CYP) aged 4-12 years was assessed by the swallowability and mouthfeel following administration of different size 3D-printed placebo tablets. Results: Using hydrocortisone as an exemplar API, Tablets were successfully produced by the FDM 3D printing process. Thermal analysis indicated that HC remained stable below 160°C and the tablets had very high mechanical strength with friability of 0%. This illustrates the ability of the printer to produce a ready-to-use-tablet without the need for a drying or finishing step. The disintegration took 9.2–14 min confirming immediate release properties. We administered for the first time globally an ingestible 3D-printed tablet to a child. CYP were able to swallow and ingest 3D-printed bi-convex tablets of either 6mm, 8mm or 10mm diameter. The 3D tablets were reported by CYP to have a slightly more discernible mouthfeel than placebo tablets of the same size manufactured in a GMP facility. Conclusion: FDM 3D printing offers a disruptive technology for the manufacture of solid dosage forms of medicines of flexible doses with excellent dose precision and pharmacopeial properties. In circumstances where modification of existing dosage forms is needed, this offers an alternative reliable means of achieving the intended dose. This technology is also suited to the manufacture of solid dosage forms of small molecules which may be particularly important in the treatment of inflammatory disease. Disclosure of Interests: None declared