Three-dimensional printing, also known as additive manufacturing, is a fabrication process whereby a 3D object is created layer-by-layer by depositing a feedstock material such as thermoplastic polymer. The 3D printing technology has been widely used for rapid prototyping and its interest as a fabrication method has grown significantly across many disciplines. The most common 3D printing technology is called the Fused Deposition Modelling (FDM) which utilises thermoplastic filaments as a starting material, then extrudes the material in sequential layers above its melting temperature to create a 3D object. These filaments can be fabricated using the Hot-Melt Extrusion (HME) technology. The advantage of using HME to manufacture polymer filaments for FDM printing is that a homogenous solid dispersion of two or more pharmaceutical excipients i.e., polymers can be made and a thermostable drug can even be introduced in the filament composition, which is otherwise impractical with any other techniques. By introducing HME techniques for 3D printing filament development can improve the bioavailability and solubility of drugs as well as sustain the drug release for a prolonged period of time. The latter is of particular interest when medical implants are considered via 3D printing. In recent years, there has been increasing interest in implementing a continuous manufacturing method on pharmaceutical products development and manufacture, in order to ensure high quality and efficacy with less batch-to-batch variations of the pharmaceutical products. The HME and FDM technology can be combined into one integrated continuous processing platform. This article reviews the working principle of Hot Melt Extrusion and Fused Deposition Modelling, and how these two technologies can be combined for the use of advanced pharmaceutical applications.

This study reports the first case of an innovative drop-on-powder (DoP) three-dimensional (3D) printing technology to produce oral tablets (diameters of 10 mm and 13 mm) loaded with an anticancer model drug, 5-fluorouracil (FLU). For this study, a composition of the powder carrier containing CaSO₄ hydrates, vinyl polymer, and carbohydrate was used as the matrix former, whereas 2-pyrrolidone with a viscosity like water was used as a binding liquid or inkjet ink. All tablets were printed using a commercial ZCorp 3D printer with modification. The resultant tablets were subject to coating with various polymeric solutions containing the drug. The composition of the polymeric solutions was adjusted at drug: polymer(s) 1:1 (w/w) ratio. Either Soluplus^® (SOL) alone or in combination with polyethylene glycol (PEG) was used to develop the coating solution of 2.5% (w/v) concentration. The particle size analysis, flow test, and particle morphology studies revealed mono-modal narrow size distribution, good flow properties, and porous loosely bound texture (of the tablets), respectively. Moreover, the advanced application of the fluorescence microscopy showed a homogenous distribution of the drug throughout the surface of the 3D printed tablets. The in vitro dissolution studies showed that the tablet compositions, dimensions, and the coating solution compositions influenced the release of the drug from the tablets. It can be concluded that our innovative DoP 3D printing technology can be used to fabricate personalized dosage forms containing optimized drug content with high accuracy and shape fidelity. This is particularly suitable for those drugs that are highly unstable in thermal processing and cannot withstand the heat treatment, such as in fused deposition modeling (FDM) 3D printing.

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.

Three-dimensional (3D) printing has recently appeared as one of the most promising additive manufacturing techniques to fabricate 3D objects, with uses spanning from engineering prototyping to medicines and cell-laden models for biomedical applications. Regardless of the type and underlying theory, 3D printing techniques involve the deposition of materials such as thermoplastic polymers or hydrogel in sequential layers one onto another to produce a 3D object. 3D printing has recently gained momentum in developing various drug delivery systems for pharmaceutical applications which is reflected by the exponential rise in the number of published papers and patents in recent years. Whilst the future of 3D printing techniques is bright, various obstacles need to be overcome before it can be applied practically in commercial-scale production. This review article discusses current approaches of altering drug delivery when manufacturing 3D printed dosage forms that vary in their drug release profiles and characteristics. Such achievements correspond to developing and delivering patient-specific treatments. With each type of 3D printing application, there are great benefits, and these are highlighted, however, a critical discussion will underline the limitations and challenges associated with 3D printing.

Background:: Fused Deposition Modelling (FDM) 3D printing has received much interest as a fabrication method in the medical and pharmaceutical industry due to its accessibility and cost-effectiveness. A low-cost method to produce biocompatible and biodegradable filaments can improve the usability of FDM 3D printing for biomedical applications. Objectives:: The feasibility of producing low-cost filaments suitable for FDM 3D printing via single screw and twin-screw hot melt extrusion was explored. Methods:: A single-screw extruder and a twin-screw extruder were used to produce biocompatible filaments composed of varying concentrations of polyethylene glycol (PEG) at 10%, 20%, 30% w/w and polylactic acid (PLA) 90%, 80% and 70% w/w, respectively. DSC, TGA and FTIR were employed to investigate the effect of PEG on the PLA filaments. Results:: The presence of PEG lowered the processing temperature of the formulation compositions via melt-extrusion, making it suitable for pharmaceutical applications. The use of PEG can lower the melting point of the PLA polymer to 170°C, hence lowering the printing temperature. PEG can also improve the plasticity of the filaments, as the rupture strain of twin-screw extruded filaments increased up to 10-fold as compared to the commercial filaments. Advanced application of FTIR analysis confirmed the compatibility and miscibility of PEG with PLA. Conclusion:: Twin-screw extrusion is more effective in producing a polymeric mixture of filaments as the mixing is more homogenous. The PEG/PLA filament is suitable to be used in 3D printing of medical or pharmaceutical applications such as medical implants, drug delivery systems, or personalised tablets.