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Background and Importance Three-dimensional (3D) printing of medicines enables precision dosing for patient populations requiring tailored dosage strengths. Compared to traditional extemporaneous compounding, 3D printing offers automated and reproducible production, ensuring accurate dosing and consistent quality. This is particularly relevant for amitriptyline, where flexible dosing is clinically important due to withdrawal risks and CYP2D6 pharmacogenomic variability. 3D printing allows dose customisation, but limited data exist on how formulation parameters affect printability and tablet quality. To guarantee consistent product performance, non-destructive analytical methods are essential for quality control.Aim and Objectives The study aims to optimise a formulation for immediate-release 3D-printed amitriptyline tablets and to develop a non-destructive NIR model. The overall goal was to create a suitable base formulation for semi-solid extrusion (SSE) printing and to gain insight in how variations in formulations affect the printability and quality of the tablets.Material and Methods Formulations containing 5, 15 and 30% (w/w) amitriptyline with 0, 5 and 10% (w/w) glycerol in a Gelucire 48/16 matrix were printed with the DoseRx1 printer. Tablets were evaluated according to the European Pharmacopoeia (EP) for uniformity of mass and dosage units, impurities and dissolution. A 5% drug load tablet was also prepared using crushed commercial amitriptyline tablets. Additionally, a non-destructive NIR-spectroscopy model was developed to predict amitriptyline and glycerol content in the tablets.Results All tablets met the specifications for uniformity of mass and dosage units and impurities. Tablets with higher drug load and higher glycerol content showed lower hardness and required larger nozzle diameters during printing. Dissolution testing showed that higher drug load tablets showed faster drug release. The tablets containing commercial amitriptyline tablets showed a slower dissolution profile compared to the equivalent dosage per tablet using pure API. The NIR model was able to predict both amitriptyline and glycerol content across the tested formulations.Conclusion and Relevance Amitriptyline was successfully 3D-printed in a Gelucire 48/16 matrix. Glycerol improved printability but decreased tablet hardness. Decreasing the amount of matrix (high drug load, pure API) accelerated dissolution. The NIR model made it possible to semi-quantify both amitriptyline and glycerol, supporting its potential as a non-destructive quality control tool. These findings provide a foundation for optimisation of 3D-printed formulations and control strategies.Conflict of Interest No conflict of interest