Three-dimensional printing (3DP) has the potential to cause a paradigm shift in the manufacture of pharmaceuticals, enabling personalised medicines to be produced on-demand. To facilitate integration into healthcare, non-destructive characterisation techniques are required to ensure final product quality. Here, the use of process analytical technologies (PAT), including near infrared spectroscopy (NIR) and Raman confocal microscopy, were evaluated on paracetamol-loaded 3D printed cylindrical tablets composed of an acrylic polymer (Eudragit L100-55). Using a portable NIR spectrometer, a calibration model was developed, which predicted successfully drug concentration across the range of 4–40% w/w. The model demonstrated excellent linearity (R2 = 0.996) and accuracy (RMSEP = 0.63%) and results were confirmed with conventional HPLC analysis. The model maintained high accuracy for tablets of a different geometry (torus shapes), a different formulation type (oral films) and when the polymer was changed from acrylic to cellulosic (hypromellose, HPMC). Raman confocal microscopy showed a homogenous drug distribution, with paracetamol predominantly present in the amorphous form as a solid dispersion. Overall, this article is the first to report the use of a rapid ‘point-and-shoot’ approach as a non-destructive quality control method, supporting the integration of 3DP for medicine production into clinical practice.

There is an increased evidence for treating hypertension by a combination of two or more drugs. Increasing the number of daily intake of tablets has been reported to negatively affect the compliance of patients. Therefore, numerous fixed dose combinations (FDCs) have been introduced to the market. However, the inherent rigid nature of FDCs does not allow the titration of the dose of each single component for an individual patient's needs. In this work, flexible dose combinations of two anti-hypertensive drugs in a single bilayer tablet with a range of doses were fabricated using dual fused deposition modelling (FDM) 3D printer. Enalapril maleate (EM) and hydrochlorothiazide (HCT) loaded filaments were produced via hot-melt extrusion (HME). Computer software was utilised to design sets of oval bi-layer tablets of individualised doses. Thermal analysis and x-ray diffractometer (XRD) indicated that HCT remained crystalline in the polymeric matrix whilst EM appeared to be in an amorphous form. The interaction between anionic EM and cationic methacrylate polymer may have contributed to a drop in the glass transition temperature (Tg) of the filament and obviated the need for a plasticiser. Across all tablet sets, the methacrylate polymeric matrix provided immediate drug release profiles. This dynamic dosing system maintained the advantages of FDCs while providing a superior flexibility of dosing range, hence offering an optimal clinical solution to hypertension therapy in a patient-centric healthcare service.

Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach.