3D Printing Solid Dosage Forms with Precisely Defined Complex Geometries for the Control of Drug
Release
M. Kyobula1, C. J. Roberts1, M. Alexander1, R. Wildman1, P. R. Gellert2
1
University of Nottingham, 2AstraZeneca
Purpose
To develop a reproducible and scalable 3D printing method for manufacturing solid dosage forms with precisely defined geometries
for the control of drug release.
Methods
Honeycomb tablets, as a model complex geometry with different cell unit sizes and solid circular tablets containing 5% w/w
fenofibrate in bees wax were produced using a piezoelectric inkjet printer mounted with a hot melt chamber. The weight and diameter
of the printed honeycombs were kept constant, the cell size was varied. Micro X-ray Computed Tomography (μCT) scanning was used
to visualise the interior structure of the honeycombs and to determine their surface area. In vitro drug release studies were performed
using a United States Pharmacopeia (USP) type II apparatus at 50rpm with 900ml of pH 7.4 phosphate buffer dissolution medium
containing 0.05M sodium dodecyl sulphate. Dissolution studies for each geometry were performed in triplicate and the drug
concentration was analysed by UV–vis spectrophotometer at 290nm.
Results
Reproducible circular solid tablets and honeycombs with different cell size were fabricated. The X-ray μCT scans (Figure 1) showed
that the honeycombs had well-defined internal cells with precisely controlled cell sizes based on the design templates applied. The
precision in geometry is due to the ability to control the spatial deposition of materials precisely and accurately when using the 3D
inkjet printing technique.
μCT scan data showed that the circular solid tablet had the lowest average surface area of 418.8 mm2 compared to the honeycombs. It
was also observed that the honeycomb (X) with larger internal cells had a smaller surface area of 1400.3 mm2 compared to 2177.3
mm2 obtained for the honeycomb (Y) with smaller cells.
In vitro drug release studies (Figure 2) showed that within 12 hours, approximately 80 % of the drug was released from the
honeycombs in comparison to 20% from the solid tablets. The honeycombs showed faster release due to the large surface area
available for the possible penetration of the dissolution medium through the beeswax matrix or possible diffusion of the drug
molecules out of the matrix during the drug dissolution process. The larger surface area honeycombs released the drug more rapidly.
Conclusion
We have established hot melting-inkjet printing can be used to fabricate solid dosage forms with complex internal geometry, which
would be extremely challenging when using existing methods such as powder compaction. Additionally, we have shown geometry
manipulation could lead to the production of a solid dosage form with variable release profiles; this could be used in the future to meet
the needs for specific patients or sub populations as related to personalised medicines or to achieve sufficient drug release for a
specific drug