(T1330-09-61) 3D Printed Medication: A Case Study on Personalization of Pediatric Arrhythmia Treatment

Purpose: The development of pediatric medication is often overlooked, leaving a scarcity of authorized dosage forms suitable for children. This issue extends to flecainide, a drug prescribed to children with abnormal heart rhythms. Current commercial tablets of 50 mg do not cater to the required dosage strength for children, necessitating the administration of an orally ingested IV-liquid containing flecainide. Unfortunately, manipulating drugs in this manner can lead to significant medication errors, posing risks to children's health. Given the narrow therapeutic dosing range of flecainide, it is crucial to ensure accurate dosage administration. This is where 3D printing of drugs can offer a potential solution. By leveraging this innovative technology, it becomes feasible to produce drugs with customizable doses and shapes. Selecting the appropriate printing technique is essential for fabricating an oral dosage form that suits the active pharmaceutical ingredient and carrier material. In this research, we explore the application of the semi-solid extrusion technique, which operates under mild conditions and low processing temperatures, to develop personalized flecainide tablets for children using 3D printing technology.

Methods: In collaboration with Erasmus Medical Center Rotterdam, TNO successfully developed a 3D printer based on the semi-solid extrusion principle. A pharmaceutical formulation comprising flecainide, poloxamer, lactose, and magnesium stearate was created. These powders were mixed using a Speedmixer™, generating a paste through particle friction-induced heat. The resulting paste was then transferred to the printer syringe, which was positioned within the 3D printer. Employing computer-aided design (CAD), we shaped the object (tablet) and developed a G-code. The tablet's design could be adjusted to achieve specific dosage strengths. Utilizing computer control, the 3D printer followed the G-code instructions, enabling the layer-by-layer formation of the tablet as the paste material was extruded from the syringe through mechanical force. To ensure clinical suitability, the 3D printed tablets were subjected to European Pharmacopoeia (EP) criteria. As there are no specific regulations for 3D printed oral dosage forms, we adhered to EP standards for tablet compounding. Our assessment included tests for uniformity of dosage units, uniformity of content, uniformity of mass, dissolution, and optional disintegration.

Results: Our research successfully yielded different flecainide tablets through 3D printing. The 3D printed tablets met the European Pharmacopoeia (EP) criteria for uniformity of mass. Furthermore, the full flecainide tablets demonstrated dissolution rates that complied with the EP's requirement of 80% dissolution within 45 minutes. We also printed a series of tablets with varying sizes, all of which satisfied EP standards for content uniformity.

Conclusion: In conclusion, we achieved successful 3D printing of flecainide tablets with varying dosage strengths. The tablets exhibited good quality and met relevant European Pharmacopoeia (EP) criteria. These 3D printed tablets will soon be made available for patient care, undergoing usage in a clinical trial. This initial use case paves the way for expanding the availability of 3D printed drugs, thereby broadening therapeutic options for children in need.

References: - Grissinger, M. (2018). Life-Threatening errors with flecainide suspension in children. Pharmacy and Therapeutics, 43(5), 258.
- van Kampen, E. E., Willemsteijn, L., & Ruijgrok, E. J. (2022). 3D printing of drugs: Expanding the options for child-tailored pharmacotherapy. Archives of Disease in Childhood, 107(10), 859-860.
- Awad, A., Trenfield, S. J., Goyanes, A., Gaisford, S., & Basit, A. W. (2018). Reshaping drug development using 3D printing. Drug discovery today, 23(8), 1547-1555.
- van Kampen, E. E., Ayyoubi, S., Willemsteijn, L., van Bommel, K. J., & Ruijgrok, E. J. (2022). The Quest for Child-Friendly Carrier Materials Used in the 3D Semi-Solid Extrusion Printing of Medicines. Pharmaceutics, 15(1), 28.

3D printed tablets from TNO built 3D printer

Concept visualization on using 3D pharma printing in a hospital pharmacy