Novel Approach to Pharmaceutical 3D-Printing Omitting the Need for Filament—Investigation of Materials, Process, and Product Characteristics

Abstract

The utilized 3D printhead employs an innovative hot-melt extrusion (HME) design approach being fed by drug-loaded polymer granules and making filament strands obsolete. Oscillatory rheology is a key tool for understanding the behavior of a polymer melt in extrusion processes. In this study, small amplitude shear oscillatory (SAOS) rheology was applied to investigate formulations of model antihypertensive drug Metoprolol Succinate (MSN) in two carrier polymers for pharmaceutical three-dimensional printing (3DP). For a standardized printing process, the feeding polymers viscosity results were correlated to their printability and a better understanding of the 3DP extrudability of a pharmaceutical formulation was developed. It was found that the printing temperature is of fundamental importance, although it is limited by process parameters and the decomposition of the active pharmaceutical ingredients (API). Material characterization including differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA) of the formulations were performed to evaluate component miscibility and ensure thermal durability. To assure the development of a printing process eligible for approval, all print runs were investigated for uniformity of mass and uniformity of dosage in accordance with the European Pharmacopoeia (Ph. Eur.).

Evaluation of Printability of PVA-Based Tablets from Powder and Assessment of Critical Rheological Parameters

“…Small batch sizes as well as small sampling sizes increase the errors found. Deviation regarding the drug content has been shown in previous studies as well [ 20 , 34 , 35 , 36 ], which might be reduced by in-line quality control mechanisms.…”

“…It was shown that vacuum compression modeling (VCM) is a useful tool for the simulation of extruded samples in order to correctly predict extrusion parameters. Also, temperature as a crucial parameter for printability was predicted by melt rheology experiments [ 20 , 33 ].…”

“…In previous studies, different approaches have been investigated to generate information regarding certain printers. Temperature as well as the closely related melt viscosity were parameters that were found to be of importance for further development [ 20 , 21 ]. Too low viscosity leads to oozing and dripping from the nozzle, reducing print quality, while too high viscosity leads to improper material flow up to a clogged nozzle or reduced layer adhesion.…”

3D Printing Direct Powder Extrusion in the Production of Drug Delivery Systems: State of the Art and Future Perspectives

“…Seoane-Viaño et al [ 29 ] also had to perform a prior step, in particular a dry granulation step, to obtain a material with sufficient flowability for the successful direct extrusion and printing of tablets using this 3D printer. This was also the case of Pflieger et al [ 30 ], who used granules previously prepared by HME as feeding material in the single-screw extrusion-based printer Flexdose TM (Digital Health Systems GmbH (Schwäbisch Gmünd, Germany)) to produce immediate-release tablets.…”

“…Pflieger et al [ 30 ] investigated the relationship between the viscosity of a material and its printability. For this purpose, they printed cylindrical tablets containing 25% w / w of metoprolol succinate and either Kollidon ® VA64 (KVA64) plasticized with polyethylenglycol (PEG) 6000 or Eudragit ® EPO and performed rheological measurements of the extruded blends using Small Amplitude Oscillatory Shear tests (SAOS).…”