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

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

doi:10.1208/s12249-018-1107-z

Shaban A Khaled, Morgan R Alexander + Show 6 more

Open Access

https://doi.org/10.1208/s12249-018-1107-z

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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 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.

Highlights

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]
Apart from surface area exposed to solution, the drug release is impacted by the inclusion of the disintegrant, NaCCS, which rapidly absorbs water and swells leading to rapid disintegration
The mesh-geometry 3D printed tablets released more than 70% of the active within 15 min achieving immediate release mesh shaped tablets

Summary

Introduction

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]. 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 offer the possibility of reducing the number of manufacturing steps as currently used in traditional tablet production process, such as powder milling, wet granulation, 1530-9932/18/0800-3403/0 # 2018 The Author(s) 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]. Other possible 3D printing methods like stereolithography (SLA) and ink-jet printing currently use excipients that are not generally recognised as safe (GRAS) [13]

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