3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets

Abstract

The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations.

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets

“…The friability revealed no variations and was demonstrated to be 0% for all the formulation. Unlike tablets generated from other 3D printed technologies such as EXT (Khaled et al, 2014a) and powder-based 3D printing (Katstra et al, 2000b;Yu et al, 2009), the friability of tablets generated using via FDM 3D printing tends to be very low or even zero (Goyanes et al, 2014a;Goyanes et al, 2015c;Pietrzak et al, 2015).…”

“…The potential of FDM 3D printing incorporating drugs into commercially available filaments (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) has been explored previously. Nonetheless, all those studies highlighted several challenges involved in employing printing technique for pharmaceutical applications.…”

“…Nonetheless, all those studies highlighted several challenges involved in employing printing technique for pharmaceutical applications. The use of elevated temperatures (185-220 • C) and limited drug loading (0.063-9.5% w/w (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) renders it less suitable for many drugs particularly thermo-labile ones. FDM 3D printing has been also restricted to a number of biodegradable thermoplastic polymers such as polylactic acid (PLA) (Sandler et al, 2014) and polyvinyl alcohol (PVA) (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) in comparison to a wide variety of choices for conventional tabletting.…”

“…FDM 3D printing has been also restricted to a number of biodegradable thermoplastic polymers such as polylactic acid (PLA) (Sandler et al, 2014) and polyvinyl alcohol (PVA) (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) in comparison to a wide variety of choices for conventional tabletting. Despite the attractive properties of PVA (Morita et al, 2000) and PLA (Hamad et al, 2016), the use of high polymer ratio in combination with the need for high molecular weight of the polymers generates polymeric matrices with limited porosity, thus resulting in extended drug release patterns (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015a;Goyanes et al, 2015b;Sandler et al, 2014;Skowyra et al, 2015).…”

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing

“…It was reported in the literature that the drug loading efficiency of the FDM 3D printed samples prepared by passive diffusion of the drug from its organic solution into the readymade placebo PVA filaments was often lower than the theoretical value by more than 15% [8,32,33]. Using a high printing temperature also can lead to unsatisfactory loading efficiency due to the thermal degradation of the drug [8,32,33].…”