Additive Manufacturing Strategies for Personalized Drug Delivery Systems and Medical Devices: Fused Filament Fabrication and Semi Solid Extrusion

Abstract

Novel additive manufacturing (AM) techniques and particularly 3D printing (3DP) have achieved a decade of success in pharmaceutical and biomedical fields. Highly innovative personalized therapeutical solutions may be designed and manufactured through a layer-by-layer approach starting from a digital model realized according to the needs of a specific patient or a patient group. The combination of patient-tailored drug dose, dosage, or diagnostic form (shape and size) and drug release adjustment has the potential to ensure the optimal patient therapy. Among the different 3D printing techniques, extrusion-based technologies, such as fused filament fabrication (FFF) and semi solid extrusion (SSE), are the most investigated for their high versatility, precision, feasibility, and cheapness. This review provides an overview on different 3DP techniques to produce personalized drug delivery systems and medical devices, highlighting, for each method, the critical printing process parameters, the main starting materials, as well as advantages and limitations. Furthermore, the recent developments of fused filament fabrication and semi solid extrusion 3DP are discussed. In this regard, the current state of the art, based on a detailed literature survey of the different 3D products printed via extrusion-based techniques, envisioning future directions in the clinical applications and diffusion of such systems, is summarized.

Keywords: 3D-Printing; FFF; SSE; additive manufacturing; customized DDS; medical devices; personalized therapy; rapid prototyping.

Figure 7

Schematic view of additive manufacturing processes according to ISO/ASTM 52,900:2021 classification [89,90], with in evidence the main AM methods applied in pharmaceutical and biomedical field [54,91].

Figure 13

Examples of 3D printed oral dosage forms produced by FFF technique. (a) Multilayer device and Duo-caplet. Adapted with permission from reference [155]; copyright (2015) American Chemical Society; (b) HME polycaprolactone-based filaments intended for 3D-printing of tablets with a lattice (“honeycomb”) structure. Reprinted with permission from reference [136]; copyright (2020) Elsevier B.V.; (c) Cardiovascular ‘Polypill’ loaded with four different drugs. Reprinted with permission from reference [159]; copyright (2018) Elsevier B.V.

Figure 1

Examples of 3D printed products for drug delivery. (a) Channeled tablet. Reprinted with permission from reference [35]; copyright (2017) Elsevier B.V. (b) Duo Tablet. Reprinted with permission from reference [36]; copyright (2017) Elsevier B.V. (c) Cube, pyramid, cylinder and sphere-shaped tablets. Reprinted with permission from reference [37]; copyright (2015) Elsevier B.V. (d) Chewable chocolate-based oral dosage forms. Reprinted with permission from reference [38]; copyright (2020) Elsevier B.V. (e) Tablets with honeycomb architectures. Reprinted from reference [39]; copyright (2017). (f) Donut-shaped tablets. Reprinted with permission from reference [40]; copyright (2016) Elsevier B.V. (g) Microneedle patch. Reprinted with permission from reference [41]. copyright (2018) Elsevier B.V.

Figure 2

Examples of 3D printed products for biomedical applications. (a) Nose-shaped device. Reprinted with permission from reference [42]; copyright (2016) Elsevier B.V. (b) Anti-biofilm hearing aids. Reprinted with permission from reference [43]; copyright (2021) Elsevier B.V. (c) Guide used during a surgery for tibial plateau fracture. Reprinted from reference [44]; copyright (2021). (d) Vaginal rings. Reprinted with permission from reference [45]; copyright (2018) Elsevier B.V. (e) 3D printed heart. Reprinted from reference [46]; copyright (2016).

Figure 3

Personalized medical approach. * Images adapted from reference [55]. ** Images adapted from reference [56].

Figure 4

Possible advantages deriving from a personalized therapy.

Figure 5

On-demand manufacturing (customized products) vs. mass manufacturing (traditional medicines, one-size-fits-all). The new scenario opened by 3DP technology.

Figure 6

3D-Printing phases to realize a printlet by FDM method. Reprinted from reference [1].

Figure 8

Ink-jet based printing technology (a) Continuous (CIJ), (b) drop-on-demand (DoD).

Figure 9

Illustration of a DOS deposition process with (a) powder bed layering system and (b) powder bed jetting system.

Figure 10

Illustration of SLS (a) and SLA (b) processes.

Figure 11

Illustration of FFF (a) and SSE (b) processes.

Figure 12

Drug loading by soaking of either preformed PLA filaments or 3D printed scaffolds. Reprinted with permission from reference [134]; copyright (2019) Elsevier B.V.

Figure 14

Examples of 3D printed medical devices produced by FFF technique. (a) Antimicrobial polycaprolactone wound dressings. Reprinted with permission from reference [165]; copyright (2017) Elsevier B.V; (b) Antibiotic loaded implants. Reprinted from reference [167]; copyright (2017). (c) Long-lasting implantable drug loaded intrauterine system. Reprinted with permission from reference [164]; copyright (2016) Elsevier B.V.

Figure 15

Examples of 3D printed oral dosage forms produced by SSE technique. (a) Polypill loaded with five different APIs. Reprinted with permission from reference [126]; copyright (2015) Elsevier B.V.; (b) Gastro-floating tablets of dipyridamole. Reprinted with permission from reference [184]; copyright (2017) Elsevier B.V; (c) Polypill designed as an osmotic pump containing captopril, and with other two compartments acting as sustained release platforms for nifedipine and glipizide. Reprinted with permission from reference [125] copyright (2015) Elsevier B.V.