Additive Manufacturing of Oral Tablets: Technologies, Materials and Printed Tablets

Abstract

Additive manufacturing (AM), also known as three-dimensional (3D) printing, enables fabrication of custom-designed and personalized 3D constructs with high complexity in shape and composition. AM has a strong potential to fabricate oral tablets with enhanced customization and complexity as compared to tablets manufactured using conventional approaches. Despite these advantages, AM has not yet become the mainstream manufacturing approach for fabrication of oral solid dosage forms mainly due to limitations of AM technologies and lack of diverse printable drug formulations. In this review, AM of oral tablets are summarized with respect to AM technology. A detailed review of AM methods and materials used for the AM of oral tablets is presented. This article also reviews the challenges in AM of pharmaceutical formulations and potential strategies to overcome these challenges.

Keywords: 3D printing; drug delivery; hydrogel; pharmaceutical; polymer; precision medicine.

Figure 1

The additive manufacturing technologies used in oral tablet fabrication.

Figure 2

Processes using different 3D printing technologies to produce 3D-printed tablets: (a) FDM printing using drug-loaded filaments produced with HME; (b) FDM printing with filaments (without APIs); (c) FDM printing using drug-infused filaments; (d) DIW of drug formulation in the form of a paste; (e) SLS printing; (f) droplet-based printing; (g) vat photopolymerization-based printing.

Figure 3

(a) FDM-printed paracetamol tablets with different geometries; paracetamol release profile from tablets in phosphate buffer (pH 6.8) with (b) 275 mm² surface area; (c) surface area to volume ratio of 1; (d) 500 mg mass. Adapted with permission from Reference [46]. Copyright 2015, Elsevier.

Figure 4

(a) DIW-printed tablets with multiple APIs (atenolol, pravastatin, ramipril, aspirin, and hydrochlorothiazide); (b) diagram of the tablet design with immediate and extended release compartments; (c) drug release profile of each drug from the tablet. Adapted with permission from Reference [138]. Copyright 2015, Elsevier.

Figure 5

(a) SLS-printed paracetamol tablets with different drug loadings (5, 20, 35 and wt%, from left to right). Tablets in the top raw were printed with Kollicoat IR and tablets in the bottom row are printed with Eudragit L100-55; (b) drug release profile from tablets printed with Kollicoat IR; (c) drug release profile from tablets printed with Eudragit L100-55. Adapted with permission from Reference [109]. Copyright 2017, Elsevier.

Figure 6

(a) SLA-printed paracetamol (top row) and 4-ASA (bottom row) tablets with different photopolymer compositions, from left to right: 35% poly(ethylene glycol) diacrylate (PEGDA)/65% poly(ethylene glycol) 300 (PEG300), 65% PEGDA/35% PEG300, and 90% PEGDA/10% PEG300; (b) drug release profile from paracetamol tablets; (c) drug release profile from 4-ASA tablets. Adapted with permission from Reference [102]. Copyright 2016, Elsevier.

Figure 7

(a) DLP-printed theophylline tablets with PEG (polyethlylene glycol) and dimethacrylate (PEGDMA) with different geometries; drug release profiles from tablets with (b) no holes; (c) two holes; (d) six holes. Adapted with permission from Reference [105]. Copyright 2019, Elsevier.

Figure 8

(a) Inkjet-printed ropinirole hydrochloride tablets; (b) drug release profile in citric acid medium (pH = 4). Adapted with permission from Reference [101]. Copyright 2017, Elsevier.

Figure 9

(a) BJ-printed Eudragit tablets; drug dissolution profiles of tablets printed with (b) Eudragit E-100; (c) Eudragit RLPO. Adapted with permission from Reference [77]. Copyright 2000, Elsevier.