The Evolution of the 3D-Printed Drug Delivery Systems: A Review

Abstract

Since the appearance of the 3D printing in the 1980s it has revolutionized many research fields including the pharmaceutical industry. The main goal is to manufacture complex, personalized products in a low-cost manufacturing process on-demand. In the last few decades, 3D printing has attracted the attention of numerous research groups for the manufacturing of different drug delivery systems. Since the 2015 approval of the first 3D-printed drug product, the number of publications has multiplied. In our review, we focused on summarizing the evolution of the produced drug delivery systems in the last 20 years and especially in the last 5 years. The drug delivery systems are sub-grouped into tablets, capsules, orodispersible films, implants, transdermal delivery systems, microneedles, vaginal drug delivery systems, and micro- and nanoscale dosage forms. Our classification may provide guidance for researchers to more easily examine the publications and to find further research directions.

Keywords: 3D printing; TTS; drug delivery systems; implant; microneedle; tablet.

Figure 1

Cross-section of the acetaminophen-containing matrix tablets based on the authors’ figure. The different colors label dissimilar compartments [30].

Figure 2

Cross-section of the constructed drug dosage forms in the article of Goyanes et al. (a) Sectioned multilayer tablet, (b) sectioned DuoCaplet (caplet in caplet) [35].

Figure 3

Cross-section of the printed polypills where three diverse compartments were created (labeled with three nonidentical colors) [36].

Figure 4

Cross-section of the polypills where ASA and HCT formulations were located in the upper immediate release compartments (labeled with blue and orange rectangles) and atenolol, pravastatin, and ramipril formulations were in three distinct extended release compartments (labeled with yellow, green, and peach blossom). The three compartments were the same size but could be visualized like this because of the original design of the “cake slice” [37].

Figure 5

Flow chart on the described tablet manufacturing methods and main breakthroughs between 1996 and 2016 [34,35,36,37,39,40,41,42].

Figure 6

Cross-section of the dual-compartmental dosage form designed by Genina et al. In the research, isoniazid (white colored) and rifampicin (red colored) were hot-melt extruded and then 3D printed into the polymeric cap (brown colored) and closed with a cap (blue colored) [46].

Figure 7

Cross-section of the 3D-printed gastro-floating tablets with 30% infill percentage rate [51].

Figure 8

Cross-section of the 3D-printed channeled tablets. Each white square represents a channel. (a) Channels parallel to the longer side; (b) channels parallel to the shorter side [52].

Figure 9

Flow chart of the described tablet manufacturing methods and main breakthroughs in 2017 and 2018.

Figure 10

Cross-section of the cylinder-shaped polypill. Each color represents diverse API-containing layers: naproxen—yellow; aspirin—purple; paracetamol—orange; caffeine—red; chloramphenicol—green; and prednisolone—blue [57].

Figure 11

Flow chart of the described tablet manufacturing methods and main breakthroughs since 2019.

Figure 12

Cross-section of the designed capsules. (a) With the same wall thickness, (b) with different wall thicknesses [120].

Figure 13

Cross-sectional design of the microneedle array [167].

Figure 14

The designed vaginal drug delivery system by our research group [178].