(224d) 3D Printing of Pharmaceuticals-Exploring Process Parameters and Structure Dry Weight Relations

Three-dimensional (3D) printing technology has added new dimensions to pharmaceutical drug product manufacturing, such as designing dosage forms with tunable drug loading, delivering pharmaceuticals on-demand, creating multi-drug pills, etc. [1, 2]. Among several 3D printing processes, micro-extrusion-based pressure-assisted microsyringe (PAM) printing is popular due to its materials (i.e., polymers, drugs, functional excipients, etc.) handling capability at low temperatures. This research explores the relationship between key process parameters and the dry weight of the 3D printed structure (i.e., printlet or tablet) to identify the optimum printing conditions. A 3-compartment tablet design was designed and developed as a dosage form considering the future application of drug tunability and multi-drug printing capability. Sodium alginate-based formulation with fenofibrate as a drug or active pharmaceutical ingredient (API) was developed and used to print. Cellink BioX 3D printer was used to print. Printing speed, printing pressure, and infill density were identified as the key process parameters and chosen as independent variables in the Box-Behnken design, a response surface methodology (RSM). The shape fidelity ranking and dry tablet weight were chosen as the dependent variables. The design was applied with 15 experiments, including three center points. Each unique experiment was performed in triplicate, making a total of 45 experimental runs. The statistical analysis and surface plots showed that pressure and printing speed have an impact compared to infill density on the dry tablet weight. Optimal values for the pressure and print speed were found to be 60 kPa and 10 mm/s, respectively. Characterization (DSC, SEM, and assay) of the tablets confirm fenofibrate crystallinity, no imperfection of the 3D printed structure, and fenofibrate content of approximately 30%, respectively.

References:

[1] M. Azad, D. Olawuni, G. Kimbell, A. Badruddoza, Md. Hossain, T. Sultana, Polymers for Extrusion-based 3D Printing of Pharmaceuticals: A Holistic Materials-Process Perspective, (review paper) Pharmaceutics, 12 (124) (2020), 1-34.

[2] I. Fleming, I. Jama, J. Chikha, D. Olawuni, G. Kimbell, M. Azad, Design & Development of 3D Printed Polymeric Structure for Pharmaceutical(s) Delivery, AIChE Annual Meeting, Abstract ID 585668, Orlando, FL, Nov. 2019.