Purpose: Current trends and challenges in the pharmaceutical industry are focused on personalized medicine as well as the identification of new treatment options for multimorbid patients. 3D printing technologies gained increasing interest over the last years since they offer several solutions to those challenges. Printing of unique patient specific tablets with an individualized dosing regimen or polypills containing several active pharmaceutical ingredients in one single tablet can increase patient compliance and therapy adherence. The fused deposition modeling technique (FDM) in particular has moved into focus as a promising production technique for 3D printed dosage forms lately. This method allows for the development of delivery systems with flexible shapes and drug release profiles. Pharmaceutical polymer filaments with adequate physical properties are required for successful product development. Today, especially the characterization of filaments used for pharmaceutical production purposes has not been standardized so far. The purpose of this study was to evaluate the suitability of methacrylic polymers for 3D printing and the identification of several analytical methods to characterize and compare those polymer filaments with commercially available filaments.
Filaments composed of EUDRAGIT® polymers (Evonik Nutrition & Care GmbH, Darmstadt, Germany) were produced using a twin screw extrusion process (Three Tec extruder ZE 9; Three-Tec GmbH, Seon, Switzerland). The produced polymer filaments were characterized and compared to commercially available non-pharma filaments utilizing three analytical methods:
The three point bend test is a common method to determine the flexural strength of a defined specimen . The test was carried out using a Texture Analyzer CT3 (AMETEK GmbH, Lorch, Germany) with a modified test holder and a 50 N load cell. The test material was placed horizontally into the holder and fixed at both ends. A controlled compression at a velocity of 1 mm/s was applied to the center of the sample (Figure 1). The maximum achievable force leading to stretching or breaking of the sample was recorded as flexural strength.
The optical appearance and surface characteristics of the polymer filaments were determined utilizing a Zeiss STEMI stereo microscope (Carl Zeiss Microscopy GmbH, Jena, Germany). To study the cross-section and appearance of the inner core of the filament, the sample was cut manually.
In addition, a printed monolayer based on previously manufactured polymer filaments was produced using a Multec M420 3D printer (Multec GmbH, Riedhausen, Germany). The monolayer printing approach provided detailed insights into the polymer performance during the 3D printing process in terms of shrinkage or warping behavior, layer adhesion properties and the overall printing quality .
Polymer filaments could be produced successfully based on several EUDRAGIT® polymers. Three analytical methods were applied to study the characteristics of the produced filaments. The results were compared to commercially available PLA filaments, which are broadly used in the plastics industry and are well suited for FDM processes. All analytical tests demonstrated a similar behavior of EUDRAGIT® based filaments in comparison to commercially available PLA filaments (Figure 1). The three point bend test showed a high flexural strength of the filament which indicates very good winding properties while providing a sufficient flexibility for the compatibility with the feeding device of the 3D printer. Microscopic pictures confirmed that the cylindrical filament surface was very smooth (Figure 2). Filaments based on EUDRAGIT® polymers could be used for printing monolayers (Figure 3) showing promising properties for printing of complex tablets. The results indicate that EUDRAGIT® based filaments provide good thermal as well as physical properties which are required for the 3D printing process.
3D printing technologies offer new opportunities for the development of pharmaceutical dosage forms. EUDRAGIT® polymers are known for their excellent performance in pharmaceutical standard processes like hot melt extrusion and coating of solid dosage forms. This study confirmed that methacrylic polymers can be applied for new emerging technologies like 3D printing. A need for comprehensive qualified analytical methods has been identified to allow for the characterization of such formulations in the future. Three analytical methods were successfully used to characterize filaments used for pharmaceutical 3D printing processes.
 https://edoc.site/din-en-iso-178-pdf-free.html, accessed 30th August 2018, DIN EN ISO178:2011-04 ‘Plastics – Determination of flexural properties (ISO 178:2010)’
Melanie Liefke– Senior Scientist Drug Delivery, Evonik Nutrition & Care GmbH, Darmstadt
Jessica Huppertz– Scientist Drug Delivery, Evonik Nutrition & Care GmbH, Darmstadt
Felix Schneider– Dipl.-Pharm., University of Greifswald, Greifswald
Peter Niepoth– Head of Applied Technologies Laboratory, Evonik Nutrition & Care GmbH, Darmstadt