This study reports a thorough investigation combining hot-melt extrusion technology (HME) and a low-cost fused deposition modelling (FDM) 3D printer as a continuous fabrication process for a sustained release drug delivery system. The successful implementation of such an approach presented herein allows local hospitals to manufacture their own medical and pharmaceutical products on-site according to their patients' needs. This will help save time from waiting for suitable products to be manufactured off-site or using traditional manufacturing processes. The filaments were produced by optimising various compositions of pharmaceutical-grade polymers, such as hydroxypropyl cellulose (HPC), Eudragit ® (RL PO), and polyethylene glycol (PEG), whereas theophylline was used as a model thermally stable drug. For the purpose of the study, twin-screw hot-melt extrusion (HME) was implemented from the view that it would result in the formation of solid dispersion of drug in the polymeric carrier matrices by means of high shear mixing inside the heated barrel. Four filament compositions consisting of different ratios of polymers were produced and their properties were assessed. The mechanical characterisation of the filaments revealed quite robust properties of the filaments suitable for FDM 3D printing of caplets (PrintCap), whereas the solid-state analyses conducted via DSC and XRD showed amorphous nature of the crystalline drug dispersed in the polymeric matrices. Moreover, the surface analysis conducted via SEM showed a smooth surface of the produced filaments as well as caplets where no drug crystals were visible. The in vitro drug release study showed a sustained release profile over 10 h where about 80% of the drug was released from the printed dosage forms. This indicates that our optimised 3D printed caplets could be suitable for the development of sustained release on-demand drug delivery systems.Polymers 2020, 12, 27 2 of 18 3D printing should be able to produce these medicines, in particular, the solid dosage forms that are adjusted according to the patient's need [3]. The use of 3D printing in producing medicines also allows hospitals and pharmacies to manufacture the medications for patients immediately after consultation. This is particularly beneficial for hospitals in remote areas so that they can supply their own patients with just-in-time medications. Apart from that, 3D printing can be used to produce dosage forms with complex shapes and different release patterns cost-effectively, which can otherwise be relatively expensive and difficult to achieve with traditional manufacturing methods [4][5][6]. It is quite difficult to produce products with high complexity via traditional pharmaceutical processes such as compression and encapsulation, and it is not effective in terms of producing personalised products [7]. With 3D printing, it is possible to fabricate medicines of different shapes, sizes, and structures to tailor the release patterns of the drug [8]. It is also more cost-effective to produce personalise...