Evaluation of 3D Printed Personalized Drug Delivery Systems Using Quality by Design Principles

Abstract

Once a 3D printed personalized dosage form has been developed, the harder and arguably more consequential question becomes whether it can be trusted, and answering that requires an evaluation framework rigorous enough to satisfy both clinicians and regulators. This study focuses squarely on the evaluation of 3D printed personalized oral drug delivery systems produced by fused deposition modelling, applying Quality by Design principles not to invent a formulation but to structure a systematic, risk-based assessment of quality. Beginning from a defined target product profile, the critical quality attributes of a personalized tablet were established, and a comprehensive evaluation was designed to test each attribute against acceptance criteria, with the influence of key variables interpreted through a design-of-experiments lens. Printed tablets across a range of infill densities and geometries were evaluated for dimensional accuracy, mass and content uniformity, mechanical strength, disintegration and dissolution behaviour, release kinetics and mechanism, drug-polymer compatibility, and physical stability under accelerated conditions. Dimensional fidelity was high and mass and content uniformity fell within acceptable limits, confirming reproducible manufacture. Drug release was strongly and predictably governed by infill density, and kinetic modelling indicated a diffusion-and-matrix mechanism consistent with the internal structure. Thermal and spectroscopic analyses confirmed that the drug remained chemically intact and dispersed within the polymer, addressing the principal thermal-stability concern of the technique, and accelerated stability testing showed the tablets retained their critical attributes over the study period. Framing the evaluation within QbD allowed the results to be interpreted not as isolated pass-or-fail tests but as evidence about a controllable design space. The study demonstrates that a QbD-structured evaluation provides the depth of quality assurance that personalized 3D printed medicines will require before clinical adoption, and highlights dissolution behaviour and stability as the attributes most deserving of ongoing control.