3D printed drug products: Non-destructive dose verification using a rapid point-and-shoot approach

David Wilsdon,Sarah J Trenfield,Martin Rowland,Simon Gaisford,Alvaro Goyanes,Abdul W Basit,Richard Telford

doi:10.1016/j.ijpharm.2018.08.002

Abstract

Three-dimensional printing (3DP) has the potential to cause a paradigm shift in the manufacture of pharmaceuticals, enabling personalised medicines to be produced on-demand. To facilitate integration into healthcare, non-destructive characterisation techniques are required to ensure final product quality. Here, the use of process analytical technologies (PAT), including near infrared spectroscopy (NIR) and Raman confocal microscopy, were evaluated on paracetamol-loaded 3D printed cylindrical tablets composed of an acrylic polymer (Eudragit L100-55). Using a portable NIR spectrometer, a calibration model was developed, which predicted successfully drug concentration across the range of 4–40% w/w. The model demonstrated excellent linearity (R2 = 0.996) and accuracy (RMSEP = 0.63%) and results were confirmed with conventional HPLC analysis. The model maintained high accuracy for tablets of a different geometry (torus shapes), a different formulation type (oral films) and when the polymer was changed from acrylic to cellulosic (hypromellose, HPMC). Raman confocal microscopy showed a homogenous drug distribution, with paracetamol predominantly present in the amorphous form as a solid dispersion. Overall, this article is the first to report the use of a rapid ‘point-and-shoot’ approach as a non-destructive quality control method, supporting the integration of 3DP for medicine production into clinical practice.

Highlights

Three-dimensional printing (3DP) has been forecast to revolutionise the pharmaceutical sector, moving away from a ‘one-size-fits-all’ treatment approach towards personalisation
3DP technology allows medicines to be tailored to the individual needs of each patient, for example, by modifying the dosage, shape, size and release characteristics, as well as via production of multi-drug combinations (Alhnan et al, 2016; Awad et al, 2018a,b; Ghosh et al, 2018; Sadia et al, 2018b; Smith et al, 2018; Trenfield et al, 2018; Verstraete et al, 2018; Zema et al, 2017)
Eudragit L100-55, which is a copolymer of methacrylic acid and ethyl acrylate (1:1 ratio) that dissolves at pH 5.5 and above, was donated by Evonik, UK

Summary

Introduction

Three-dimensional printing (3DP) has been forecast to revolutionise the pharmaceutical sector, moving away from a ‘one-size-fits-all’ treatment approach towards personalisation. All of the 3DP technologies follow the 3 D’s of 3D printing (Trenfield et al, 2018); a) design: computer aided design software is used to create the dosage form; b) develop: the selected drug(s) and polymer(s) are blended and loaded into the 3D printer and c) dispense: the 3D dosage form is fabricated, in a layer by layer manner, to meet the design requirements. A medicine could be designed to meet the patient’s

Objectives

Methods

Results