In Vitro Tests of FDM 3D-Printed Diclofenac Sodium-Containing Implants

Abstract

One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and biocompatibility investigations. Our objective was to manufacture implantable drug delivery systems using fused deposition modeling, and in vitro tests were performed for the assessment of these products. Polylactic acid, antibacterial polylactic acid, polyethylene terephthalate glycol, and poly(methyl methacrylate) filaments were selected, and samples with 16, 19, or 22 mm diameters and 0%, 5%, 10%, or 15% infill percentages were produced. The dissolution test was performed by a USP dissolution apparatus 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye (MTT)-based prolonged cytotoxicity test was performed on Caco-2 cells to certify the cytocompatibility properties. The implantable drug delivery systems were characterized by thermogravimetric and heatflow assay, contact angle measurement, scanning electron microscopy, microcomputed tomography, and Raman spectroscopy. Based on our results, it can be stated that the samples are considered nontoxic. The dissolution profiles are influenced by the material properties of the polymers, the diameter, and the infill percentage. Our results confirm the potential of fused deposition modeling (FDM) 3D printing for the manufacturing of different implantable drug delivery systems in personalized medicine and may be applied during surgical interventions.

3D Printing of Thermo-Sensitive Drugs

“…For instance, Petra et al successfully printed implants using four different polymers: polylactic acid (PLA), antibacterial PLA (Anti), polyethylene terephthalate glycol (PETG), and poly(methyl methacrylate) (PMMA). The model drug, diclofenac, was poured manually by stopping the process followed by printing of the top layers [ 45 ]. The technique was also used for the fabrication of 3D-printed wafers loaded with nanostructured lipid carriers (NLCs) of quercetin and piperine.…”

“…FDM is the most widely evaluated 3D printing technique in the pharmaceutical sector, owing to the use of a relatively straightforward process and less expensive equipment, a diverse choice of excipients, and ease of producing dosage forms. Many dosage forms including tablets, polypills, controlled-release devices, and oro-mucosal films have been fabricated using this technique [ 43 , 44 , 45 , 46 ]. The main drawback of FDM is the possible risk of drug degradation that may result from the use of a significant amount of heat.…”

3D-Printing of Drug-Eluting Implants: An Overview of the Current Developments Described in the Literature

“…These methods are often very time-consuming and only porous structures [ 67 , 68 ] enable the possibility of suitable drug concentrations in the inner parts of the implant. Other, more exceptional, postprinting drug loading mechanisms are the incubation of implants with sublimated iodine [ 73 ], drug loading with supercritical carbon dioxide [ 74 ] or the manually filling of powdered drug or drug-loaded alginate gel into previously 3D-printed hollow or reservoir structures [ 75 , 76 , 77 , 78 ].…”

“…The shape of a 3D-printed object depends on the predefined computer-created design and is adjustable from simple to complex geometries. Proof-of-concept studies often use simple designs like discs, cylinders or cuboids [ 37 , 58 , 71 , 74 , 78 , 141 , 142 ] for the demonstration of the performance of 3D-printing for implants, such as antibacterial efficacy or controllable drug release, by varying implant properties [ 37 , 50 , 58 , 66 , 78 , 141 ].…”

“…Furthermore, the studies of Arany et al [ 78 ] demonstrated the effects of different polymers, sizes and infill ratios on drug release behavior. In this study, the printed dosage forms were cylindrical containers which were used as carriers for the powdered drug, which was manually inserted before the top layers of the carrier were printed.…”