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

Abstract

The idea that every patient should receive a dose tailored specifically to them has long been appealing in principle and almost impossible to deliver in practice, because conventional tablet manufacturing is built around enormous batches of identical units. Three-dimensional printing changes that equation by making it economically feasible to produce single tablets, or small runs, each with a bespoke dose, geometry, and release profile. This study reports the development and evaluation of 3D printed personalized drug delivery systems built around Quality by Design principles, using fused deposition modelling to fabricate oral tablets from a model drug dispersed in a thermoplastic polymer matrix. Rather than optimising by trial and error, we defined a target product profile, identified the critical quality attributes that matter for a personalized tablet, and mapped the critical material attributes and process parameters that influence them. A design of experiments approach, specifically a Box-Behnken response surface design, was used to study the effect of infill density, printing temperature, and polymer-to-drug ratio on drug release, mechanical strength, and printability. The resulting models were statistically significant and allowed a design space to be defined within which quality could be assured. Optimised tablets released drug in a predictable, tunable manner, with infill density emerging as the dominant lever over release rate, and mechanical properties remained within acceptable limits across the design space. Printed tablets showed uniform mass and content, reproducible dimensions, and drug-polymer compatibility confirmed by thermal and spectroscopic analysis. The work demonstrates that coupling 3D printing with a formal QbD framework yields personalized dosage forms that are not only flexible but also systematically understood and controllable, which is precisely what regulators and clinicians would require before such systems could reach patients. Limitations around drug thermal stability and throughput are discussed.