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 for 3DP) of consistent diameter may be challenging and time consuming by hot melt extrusion. Additionally, to implement non-destructive quality control (QC) methods for 3DP tablets requires producing tablets containing varying levels of active pharmaceutical ingredient for model calibration.

Highlights

VCM technology supports personalised medicines development via FDM 3D printing.

Pharma-ink of dimensional accuracy for FDM printing produced by new VCM technology.

Small-scale VCM setup reduces material requirements for FDM printing development.

25 % drug loading was achieved with new VCM pharma-ink workflow.

VCM tablets as calibration surrogates for quantitative NIR predictions on printlets.

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 3DP 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 for 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 Pressure Liquid Chromatography. This work demonstrates the synergies between VCM and FDM printing for expediting the development of personalised oral medicines with enhanced material sustainability.

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Materials

Tamoxifen citrate (TC) (MW: 563.6 g/mol) was obtained from Hepartex® (Saint-Cloud, France), hydroxypropylcellulose (Klucel ELF; MW: 40,000) and polyvinylpolypyrollidone (Polyplasdone-XL) from Ashland Industries Europe GmbH (Schaffhausen, Switzerland), and d-Mannitol from Scientific Laboratory Supplies Ltd. (Nottingham, United Kingdom). Sodium phosphate monobasic monohydrate (NaH2PO4·H2O), magnesium stearate (MgSt) (technical grade), N,N-dimethyloctylamine (DMOA), acetonitrile (ACN), and 5 M hydrochloric acid (HCl) were purchased from Sigma Aldrich (Gillingham, United Kingdom) while phosphoric acid (for HPLC) was purchased from Thermo Fisher Scientific (Cheshire, United Kingdom). Materials were used as received unless otherwise stated.

2.2.2. Preparation of pharma-ink

The pharma-ink, in this case drug loaded filaments, were prepared using VCM and a filament moulder systems (MeltPrep GmbH, Graz, Austria). Firstly, ca. 2.3 g of formulation was transferred to the VCM Disc Tool D25 (25 mm diameter) lined with polytetrafluoroethylene (PTFE) foils (MeltPrep GmbH, Graz, Austria) and compressed at 110 °C under vacuum for five min. The compressed disc was cooled to room temperature under continued vacuum. The resulting VCM disc was placed inside a PTFE lined D25 (25 mm diameter) feed chamber for the filament moulder connected to a PTFE tube of 1.75 mm internal diameter (MeltPrep GmbH, Graz, Austria) fitted inside the filament moulder channel. The filament was manufactured at 130 °C and vacuum pressure for 20 min and cooled to room temperature under continued application of vacuum. Cooled filament was liberated from the PTFE tube by passing through a tube cutter (MeltPrep GmbH, Graz, Austria). The equipment produces pharma-ink of up to 1 m in length, and ca. 90 cm long pharma-ink was produced per batch. An overview of the working principles of the instrument have been provided in Fig. 1. The diameter of the prepared filament was validated using a digital Vernier calliper (GNW Instrumentation, Southport, UK) at three separate sections.

Anna Kirstine Jørgensen, Ye Chan Oh, Hanxiang Li, Daniel Treffer, Maryam Parhizkar, Alvaro Goyanes, Abdul W. Basit, Expediting 3D printed medication development using vacuum compression moulding, Journal of Controlled Release, 2025, 113766, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2025.113766.