Category: Formulation and Quality
Purpose: Three-dimensional printing is forecast to cause a paradigm shift in pharmaceuticals, moving away from a ‘one-size-fits-all’ approach towards on-demand personalization. Before clinical integration is feasible, a number of challenges remain relating to final product quality control (QC) and safety. Conventional QC assays are destructive, expensive and laborious which would be wholly unsuitable for real-time batch release. It is clear that the development of non-destructive and rapid dose verification and characterization methods are required to ensure final product quality1.This project aimed to evaluate the use of near infrared (NIR) and Raman spectroscopy as quality control methods on 3D printed tablets (printlets).
Methods: A portable reflectance NIR spectrometer for dose predictions was evaluated on printlets produced using selective laser sintering (SLS). Printlets were drug loaded with 4-40% w/w of acetominophen, and printed with different geometries (films, cylindrical and tori shapes) and excipients (Eudragit L100-55 and HPMC). Printlets were scanned at six points using NIR and averaged for calibration model development using partial least squares (PLS) regression. Data analysis was performed using MATLAB R2017a with the PLS Toolbox v 8.6 (Eigenvector, USA) and the predictive performance was compared with conventional HPLC analysis. Raman microscopy (InVia confocal Raman microscope, Renishaw, UK) was used to evaluate drug distribution and phase (785 nm laser, 100% laser power, 100-3200cm-1).
Results: For the first time, we report the development of a novel method enabling an at-line quantification of dosage as a non-destructive QC method for 3D printed tablets. SLS printed tablets were successfully designed and produced with different geometries (films, cylindrical and tori shapes, Figure 1). The developed PLS model was fully validated according to regulatory guidance2, demonstrating excellent linearity (R2 = 0.996), precision (RSD < 2%) and accuracy (RMSEP = 0.63%) for dose prediction across the range of 4-40% w/w (Figure 2). High accuracy was maintained for printlets of a different geometry (torus shapes; RMSEP = 2.05%), a different dosage form (oral films; RMSEP = 1.14%) and with alternative excipients (RMSEP = 1.36%). Raman microscopy showed a homogenous drug distribution, with acetominophen predominantly present in the amorphous form as a solid dispersion (Figure 3).
Conclusion: Overall, this research 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 personalised medicine production into clinical practice.
Alvaro Goyanes– FabRx, London, England, United Kingdom
Richard Telford– Bradford, England, United Kingdom
David Wilsdon– Sandwich, England, United Kingdom
Martin Rowland– Principal Scientist, Pfizer Ltd., Sandwich, England, United Kingdom
Simon Gaisford– Professor, UCL School of Pharmacy, London, England, United Kingdom
Abdul Basit– Professor, UCL School of Pharmacy, London, England, United Kingdom