Extrusion 3D printing of paracetamol tablets from a single formulation with tunable release profiles through control of tablet geometry

Khaled, Shaban A.; Alexander, Morgan R.; Irvine, Derek J.; Wildman, Ricky D.; Wallace, Martin J.; Sharpe, Sonja; Yoo, Jae; Roberts, Clive J.

Abstract

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, breaking force and were within acceptable range as defined by the international standards stated in the United States 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.

Citation

Khaled, S. A., Alexander, M. R., Irvine, D. J., Wildman, R. D., Wallace, M. J., Sharpe, S., Yoo, J., & Roberts, C. J. (2018). Extrusion 3D printing of paracetamol tablets from a single formulation with tunable release profiles through control of tablet geometry. AAPS PharmSciTech, 19(8), 3403–3413. https://doi.org/10.1208/s12249-018-1107-z

• Journal Article Type: Article
• Acceptance Date: Jun 12, 2018
• Online Publication Date: Aug 10, 2018
• Publication Date: 2018-11
• Deposit Date: Jul 9, 2018
• Publicly Available Date: Aug 20, 2018
• Journal: AAPS PharmSciTech
• Electronic ISSN: 1530-9932
• Publisher: American Association of Pharmaceutical Scientists
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 8
• Pages: 3403–3413
• DOI: https://doi.org/10.1208/s12249-018-1107-z
• Public URL: https://nottingham-repository.worktribe.com/output/938069
• Publisher URL: https://link.springer.com/article/10.1208/s12249-018-1107-z
• Contract Date: Aug 20, 2018