Research Article: Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with Tunable Release Profiles Through Control of Tablet Geometry

Date Published: August 10, 2018

Publisher: Springer International Publishing

Author(s): Shaban A. Khaled, Morgan R. Alexander, Derek J. Irvine, Ricky D. Wildman, Martin J. Wallace, Sonja Sharpe, Jae Yoo, Clive J. Roberts.


An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (> 80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.

Partial Text

Personalised medicine is defined as a customization of health care to individual patients through linking diagnostics and treatments with genetic testing and emerging technologies such as proteomics and metabolomics analysis (1). The main advantages of this approach are to increase the effectiveness of the prescribed treatment regimen and to minimise their adverse effects such as those linked to overdosing of drugs with a narrow therapeutic index such as digoxin and anti-clotting agents (2). In the context of solid oral dosage forms, conventional large-scale tableting manufacturing methods are clearly unsuited to personalised medicine and, in addition, provide restrictions on the complexity achievable in the dosage form in terms of, for example, tablet geometry, drug dosage, distribution and combinations. 3D printing offers the potential for the manufacture of bespoke solid oral dosage forms. 3D printers also offer the possibility of reducing the number of manufacturing steps as currently used in traditional tablet production process, such as powder milling, wet granulation, dry granulation, tablet compression and coating and the potential for rapid formulation development with limited quantities of active ingredients as available in early drug development (3,4).

Extrusion-based 3D printing of different paracetamol tablet geometries with a high drug loading (81% w/w) was successfully demonstrated. The mesh-geometry 3D printed tablets released more than 70% of the active within 15 min achieving immediate release mesh shaped tablets. In contrast, only 25 and 12% of the drug was released in the same period from the ring and the solid paracetamol tablets, respectively, effectively demonstrating sustained release. Drug release from the tablets showed a clear dependency on the SA/V ratio. XRPD, FTIR and DSC data show that the paracetamol form was unaffected by the printing and that there were no detectable interactions between the paracetamol and the chosen excipients (starch, PVP K25 and NaCCS). The 3D printed paracetamol tablets were also evaluated for weight variation, drug content in the final tablets, hardness, friability and tablet dimensions and were within acceptable range as defined by the international standards stated in the USP. This work again validates that the extrusion-based 3D printing process is capable of producing viable tablets from materials having compendia grades available for pharmaceutical applications. More importantly this work demonstrates for the first time the application of extrusion-based printing for tailoring of drug release from a single formulation through control of only tablet geometry the first. We believe this is a significant step forward in the potential wider take up of 3D printing for the manufacture of medicines, particular in the areas of clinical development and personalised medicines. With this principal demonstrated, it becomes possible to envisage control of drug release and dose (through dosage form size) on an individual basis using a 3D printer, without the need for forming complex mixtures from different formulation ‘cartridges’. This would greatly simplify potential supply chains of formulation inks and the quality control of the printed product.