(T1230-08-53) Investigation of the Internal Porosity and Drug Release Profile of Screw-Based 3D-Printed Bupropion Tablets

Purpose: Hot-Melt Extrusion (HME) has gained recognition as an innovative processing method for producing molecular dispersions of active pharmaceutical ingredients within various polymer and/or lipid matrices. This approach has enabled the development of drug delivery systems with controlled, modified, extended, and targeted release profiles [1]. In the present study, HME was used to prepare three different filament formulations. Each formulation contained 30% bupropion (BUP) as the active ingredient, and 60% of different grade of Ethylcellulose (7N, 10N and 20N), with 10% xanthan gum as excipients. The resulting filaments were then chopped into small pieces using a pelletizer. The produced pellets were subsequently used in a screw-based direct extrusion 3D printer to fabricate tablets of two different sizes: 10×10×3mm and 13×13×2mm (length, width, and height, respectively). A morphological analysis of the 3D printed tablets before and after dissolution was performed by means of high-resolution X-Ray micro–Computer Tomography (microCT) without destroying the sample. The dissolution test was carried out under biorelevant conditions to simulate gastrointestinal transit. These conditions allowed for the assessment of drug release kinetics and the potential bioavailability of the developed formulations under physiologically relevant pH transitions.

Methods: The 3D printed tablets (10x10x3 mm) of all the investigated formulations (7N, 10N and 20N) were scanned using a Skyscan 1272 micro-CT scanner (Bruker, Belgium), with a pixel size of 6.3 μm and a rotation step of 0.2° over a full 360° rotation. The captured images were reconstructed using the NRecon software (Bruker, Belgium). Uniform reconstruction parameters were applied to all samples, including ring artefact and beam hardening correction to ensure consistent image quality. For the quantification of the total porosity, the reconstructed images were analysed using the CT-Analyser (CTAn) software. Finally, to qualitatively evaluate the samples’ microarchitecture and structural changes before and after dissolution, the CT-Voxel (CTVox) software was used for 3D visualisation. Thermogravimetric analysis (Q5000, Thermal Instruments, Moraine, OH, USA) was performed to determine the decomposition temperature of BUP to identify the maximum processing temperature that can be used during HME and 3D printing while maintaining BUP stability. The release of BUP from each formulation was tested using a USP II dissolution paddle apparatus (PharmaTest-D17, Hainburg, Germany) at 50 rpm and 37 ± 0.5 °C in aqueous dissolution media (initially in an acidic medium (pH 1.2) to mimic the gastric environment, followed by testing at a pH 6.8 buffer solution to simulate intestinal conditions).

Results: TGA showed that the degradation temperature of BUP was 170 °C, so HME and 3D printing were performed below this temperature. X-Ray microCT was employed to qualitatively and quantitatively evaluate the internal structure and porosity of the samples of all studied syntheses, before and after dissolution. The total porosity for all samples is presented in the Table, where it shown that before-dissolution the 3D printing process has a pronounced effect on the internal porosity of the tablets. After printing, the tablets featured internal pores at the sites where adjacent rasters coalesce. This is an innate characteristic in FDM printed structures [2] and is dependent on the printing parameters such as printing temperature, the environmental conditions during printing and cooling as well as the physical characteristics of the semi-molten material as it is deposited (e.g. viscosity). The variations in internal porosity across the different preparations are minimal and can be mainly attributed to the material properties, since the printing parameters were maintained identical for all compositions. Nonetheless, after dissolution, the porosity of the tablets was found to differ significantly and was highly dependent on the material composition. The 7N tablets featured the highest porosity of almost 20%, indicating higher dissolved volume. The 20N tablets, although featuring the highest internal porosity before dissolution, showed the fewest cavities after dissolution.  Alterations in overall tablet morphology were also observed, attributed to the swelling and subsequent deswelling of the tablets after drying. These results were consistent with the release profile, as the tablets containing the lower molecular weight Ethylcellulose (7N) showed higher release, followed by 10N and 20N, with the latter having the lowest. Tablets with dimensions 13×13×2 mm showed higher release compared to those of 10×10×3 mm.

Conclusion: X-ray microCT analysis revealed that the FDM 3D printing process inherently introduces internal porosity due to raster coalescence, largely independent of material composition when identical printing parameters are used. However, post-dissolution porosity varied significantly among formulations and was strongly influenced by the ethylcellulose molecular weight. Tablets with lower molecular weight ethylcellulose (7N) exhibited the highest post-dissolution porosity and drug release, whereas 20N tablets retained their structure more effectively. Additionally, tablet geometry impacted release, with 13 × 13 × 2 mm tablets showing greater release compared to 10 × 10 × 3 mm. These findings highlight the combined influence of material properties and tablet design on drug release behavior.

References: 1. Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A Review of Hot-Melt Extrusion: Process Technology to Pharmaceutical Products. ISRN Pharm. 2012;2012:1–9.
2. Garzon-Hernandez S, Garcia-Gonzalez D, Jérusalem A, Arias A. Design of FDM 3D printed polymers: An experimental-modelling methodology for the prediction of mechanical properties. Mater Des [Internet]. 2020;188:108414. Available from: https://doi.org/10.1016/j.matdes.2019.108414

Acknowledgements: The authors gratefully acknowledge support from the National Recovery and Resilience Plan 'Greece 2.0', funded by the European Union – NextGenerationEU. Acknowledge the Hellenic Foundation for Research and Innovation (HFRI) under the 5th Call for HFRI PhD Fellowships grant for their support.

The porosity (%) before and after the dissolution of the three different grades of Ethylcellulose

The pictures before and after dissolution of the three different grades of Ethylcellulose taken by the X-ray microCT

The dissolution profiles of three Ethylcellulose grades formulated in two tablet sizes.