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.

Despite the abundant use of polyethylene oxides (PEOs) and their integration as an excipient in numerous pharmaceutical products, there have been no previous reports of applying this important thermoplastic polymer species alone to fused deposition modelling (FDM) 3D printing. In this work, we have investigated the manufacture of oral doses via FDM 3D printing by employing PEOs as a backbone polymer in combination with polyethylene glycol (PEG). Blends of PEO (molecular weight 100K, 200K, 300K, 600K or 900K) with PEG 6K (plasticiser) and a model drug (theophylline) were hot-melt extruded. The resultant filaments were used as a feed for FDM 3D printer to fabricate oral dosage forms (ODFs) with innovative designs. ODFs were designed in a radiator-like geometry with connected paralleled plates and inter-plate spacing of either 0.5, 1, 1.5 or 2 mm. X-ray diffraction patterns of the filaments revealed the presence of two distinctive peaks at 2θ = 7° and 12°, which can be correlated to the diffraction pattern of theophylline crystals. Varying blends of PEO and PEG allowed the formation of mechanically resistant filaments (maximum load at break of 357, 608, 649, 882, 781 N for filament produced with PEO 100K, 200K, 300K, 600K or 900K, respectively). Filaments of PEO at a molecular weight of 200-600K were compatible with FDM 3D printing process. Further increase in PEO molecular weight resulted in elevated shear viscosity (>10 4 Pa.S) at the printing temperature and hindered material flow during FDM 3D printing process. A minimal spacing (1 mm) between parallel plates of the radiator-like design deemed essential to boost drug release from the structure. This is the first report of utilising this widely used biodegradable polymer species (PEOs and PEG) in FDM 3D printing.

BackgroundDespite regulatory advances, lack of age-appropriate formulations (AAFs) remains a challenge in paediatric practice. 3D-printing of oral dosage forms (ODFs) offers potential for AAFs for children. Optimising drug release from 3D-printed ODFs is an important technological step. Despite the abundant use of polyethylene oxides (PEOs) and their extensive use as an excipient, there have been no previous reports of applying this thermoplastic polymer species alone to fused deposition modelling (FDM) 3D printing. We assessed the impact of polymer molecular weight (MW) on the mechanical properties of the resultant filaments and their rheological properties. In the FDM 3D printing process, we also tested the effect of an innovative radiator-like design of the ODF on the acceleration of drug release patterns.MethodsBlends of PEO (MW: 100K, 200K, 300K, 600K or 900K) with PEG 6K (plasticiser) and a model drug (theophylline) were prepared by hot-melt extrusion. The resultant filaments were used as a feed for a FDM 3D printer to fabricate innovative designs of ODFs in a radiator-like geometry with inter-connected paralleled plates and inter-plate spacing of either 0.5mm, 1mm, 1.5mm or 2mm.ResultsVarying blends of PEO and PEG allowed formation of mechanically resistant filaments (maximum load at break of 357, 608, 649, 882, 781 N for filament produced with 100K, 200K, 300K, 600K or 900K, respectively). Filaments of PEO at a MW of 200K-600K were compatible with FDM 3D printing. Further increase in PEO MW resulted in elevated shear viscosity (>104 Pa.S) at the printing temperature and hindered material flow during FDM 3D printing. A minimum spacing (1 mm) between parallel plates of the radiator-like design was essential to boost drug release from the structure.ConclusionThese findings are essential in the development of next-generation personalised drug delivery doses using specialised polymer/polymer blends purposely optimised for FDM 3D printing.Disclosure(s)Nothing to disclose