Expediting 3D printed medication development using vacuum compression moulding

Abstract

Three-dimensional printing (3DP) is a disruptive technology for producing medications tailored to individual patients, with fused-deposition modelling (FDM) being one of the most established technologies for clinical implementation. However, obtaining FDM pharma-ink (drug-loaded filaments) of consistent diameter may be challenging and time consuming by hot melt extrusion. Additionally, to implement non-destructive quality control methods for 3DP tablets requires producing tablets containing varying levels of active pharmaceutical ingredient for model calibration. Some of these levels may not be possible to manufacture due to impaired formulation processability. Here, vacuum compression moulding (VCM) melt-processing was deployed for assessing two aims for 3DP of personalised oral tablets. First, as a novel small-scale production method for dimensionally accurate pharma-ink, and second, accomplishing non-destructive dose verification in 3DP tablets with a model derived from VCM object samples acting as 3DP tablet surrogates. Tablets containing 10, 20, and 30 mg tamoxifen, a drug currently being progressed in 3DP clinical trials, were accurately printed with the developed pharma-ink, with mass and drug content variations within European and U.S. pharmacopoeia specifications. Release profiles were equal between tablet sizes. For the first time, the feasibility of cylindrical VCM objects as tablet surrogates was demonstrated for non-destructive near-infrared (NIR) dose determination in 3DP tablets. The NIR model calibrated with VCM samples displayed excellent linearity and robustness (R² = 0.997 and R²_{cross validation} = 0.996) with no statistical difference in predicted tamoxifen dose for the tablets as compared to high performance liquid chromatography. This work demonstrates the synergies between VCM and FDM printing for expediting the development of personalised oral medicines with enhanced material sustainability.

Keywords: Chemometrics for drug quantification; Extrusion-based 3D printing; Fused filament fabrication additive manufacturing; Pharmaceutical fused deposition modeling; Process analytical technology and quality control; Sustainable personalized molded printlets; Vacuum compression molding.