Development of immediate release (IR) 3D-printed oral dosage forms with focus on industrial relevance.

Pharmaceutical 3D-printing represents a potentially new dosing and manufacturing approach for the pharmaceutical industry, with unique opportunities for personalization of dosage strengths. Fused deposition modelling (FDM) is a 3D-printing technique, which presents advantages for decentralized on-site manufacturing in hospitals and pharmacies. This study introduces industrially relevant development of formulations for filaments with the required mechanical properties to be 3D-printable and providing immediate release (IR) dosage forms using safe materials approved also for pediatric use. Hydroxypropyl-cellulose (HPC) SSL was chosen as hydrophilic polymer and caffeine with a load of 5-20% as thermally stable model drug. Poly-(vinyl pyrrolidone-vinyl acetate) copolymer (Kollidon VA64) and poly-(vinyl alcohol-polyethylene glycol) graft copolymer (Kollicoat IR) were additional water-soluble polymers tested in combination with HPC and xylitol and polyethylene glycol (PEG) 4000 were evaluated as hydrophilic plasticizers and PEG4000 and maltodextrin as pore formers. Formulations were hot-melt extruded using a scalable twin-screw extruder and 3D-printed into honeycomb geometry solid dosage forms with high (100%) and low (80%) infill density. Rapid or very rapid release was achieved via formulation selection and tablet design parameters. PEG4000 in combination with Kollidon VA64 demonstrated superior processability and significantly accelerated release properties of the matrix independently of infill density. Lowering caffeine content improved hot-melt extrusion processability for each formulation but prolonged dissolution. The use of Kollicoat IR resulted in superior mechanical properties of the manufactured filaments, with easy handling and successful 3D-printing for drug load of 5 to 20%. For most formulations, lowering infill density of 3D-printed tablets yielded faster drug dissolution in agreement with the literature. However, the extent of the infill density effect varied depending on formulation. Caffeine was present in stable crystalline state in 3D-printed tablets. Printing temperature appeared to be critical for drug dissolution in vitro. This wide-ranging excipient investigation epitomizes the beginning of a toolbox approach targeting FDM processability in combination with immediate release characteristics of personalized dosage forms.