Fanous, Marina, Gold, Sarah, Muller, Silvain, Hirsch, Stefan, Ogorka, Joerg and Imanidis, Georgios (2020) Simplification of FDM 3D-Printing paradigm: feasibility of 1-step Direct Powder Printing for Immediate Release dosage forms production. International journal of pharmaceutics. ISSN 1873-3476; 0378-5173

Abstract

Three-dimensional (3D)-printing of tablets via fused deposition modelling (FDM) is gaining attention for the production of flexible and personalized dosage forms. FDM presents advantages for decentralized on-site manufacturing in hospitals and pharmacies as no powder or solvents are involved in the printing process and post-processing can be avoided. However, the current FDM paradigm for dosage forms development is complex, and involves a hot-melt extrusion step and 3D printable drug-loaded filaments as intermediate products for tablet manufacturing.
In this study, simplification of the current FDM set-up for rapid release dosage forms manufacturing was explored. Several powder blends were directly loaded into a cartridge-like head and were successfully printed directly with honeycomb design following heating of the extrusion cartridge. This served as a proof of concept for 1-step direct powder printing (DPP) with incorporation of in-built porosity allowing higher surface area.
A heat processable, water soluble polymer, Hydroxypropylcellulose (HPC) SSL was chosen as rapid release matrix former and caffeine (10%) as thermally stable model drug. The effect of incorporation of a plasticizer/pore former (PEG4000) and a rapidly dissolving polymer (Kollidon VA64) on DPP processability and dissolution profiles was investigated. Formulations were directly 3D-printed into solid dosage forms with high (80%) and low (30%) infill density, and critical quality attributes analyzed (e.g. dissolution profiles, chemical stability and physical form).
The obtained directly 3D-printed tablets demonstrated good weight and content uniformity. Low infill density tablets showed rapid release dissolution profiles independently of the formulation, whereas for high infill density tablets a combination of pore-former PEG4000 and rapidly-dissolving polymer Kollidon VA64 was required to achieve rapid release. Caffeine was found in crystalline state and in the desired polymorph in directly 3D-printed tablets.
Direct Powder 3D-printing feasibility for immediate release dosage forms manufacturing was demonstrated. This technique might create an opportunity to skip the hot-melt extrusion step, allowing 3D-printing independent of mechanical properties of a filament. This might potentially prolong formulation shelf life as thermal stress is applied only once, shortly before the tablets production and dispensing. Moreover, this powder-in-a-cartridge technique might create a future opportunity for decentralized production: loading powder formulation in a cartridge at the industrial facility, and 3D-printing on clinical site potentially using in the same 3D-printer for implants, tablets and even tissues and organs.

Item Type:	Article
Date Deposited:	20 Feb 2020 00:45
Last Modified:	20 Feb 2020 00:45
URI:	https://oak.novartis.com/id/eprint/40738