Interview with Dr. Julian Quodbach, Institute for Pharmaceutical Technology and Biopharmacy, Heinrich Heine University Düsseldorf
Exclusively for K-MAG
Source: TH Köln
3D printing can be used to produce versatile, individual shapes. This type of extrusion process is therefore not only popular in the plastics industry – it is also suitable for medical technology applications. Only the right polymers have to be found first.
In an interview with K-MAG, Dr. Julian Quodbach talks about the state of research on pharmaceutical polymers today and what makes them so difficult to use for 3D printing medicines.
What are pharmaceutical polymers?
Dr. Julian Quodbach: Pharmaceutical polymers can be synthetic polymers or derivatives of natural polymers, for example cellulose ethers or starch derivatives. There is a certain range of pharmaceutical polymers that have to meet different requirements than conventional polymers. They must not be toxic, must be able to be broken down in the body depending on their use and must have a purity that polymers for a technical application often do not require.
Why do new pharmaceutical polymers need to be developed for printed drug research?
Quodbach: We are looking particularly at the fused deposition modelling (FDM) process: This is about how polymers with active ingredients are made into filaments via an extrusion process, which are then printed. The problem with this process is that, on the one hand, the processing temperatures of most pharmaceutical polymers are high, which in turn results in thermal instability of the active ingredients – when active ingredients are heated to 200 degrees Celsius, there is often nothing left of the active ingredient afterwards.
Another problem is the filament itself: It needs certain mechanical properties so that it can be 3D-printed.
The development of new polymers for this application is being carried out in the project "PolyPrint – Printable Polymer Drug Filaments for Individual Oral Drug Dosage", which is funded by the German Federal Ministry of Education and Research. Merck is working very intensively on the development and has already handed over a first generation of polymers that can be extruded at lower temperatures and are more printable. This is now to be improved even further in a second generation of polymers.
Exhibitors and products around extruders and additive manufacturing:
Who was involved in the interdisciplinary work and in which way?
Quodbach: In addition to HHU, three other partners are involved: the Laboratory for Manufacturing Systems from the Cologne University of Applied Sciences, which is working on the design of a new 3D printer that is specifically suitable for printing medicines. Conventional 3D printers based on the FDM principle, with their open axis systems or filament residues in the print head, are not well suited for printing pharmaceuticals, because contamination between different active ingredients must be avoided.
We also have Merck, which is mainly involved in the synthesis of new polymers and scaling up promising candidates so that we can work directly on a larger scale. Another department at Merck is investigating the pharmaceutical application of these polymers in initial studies.
The third partner is the company Gen-Plus, which primarily contributes analytical developments and conducts stability studies for the polymer-drug combinations.
What does HHU's involvement in research look like?
Quodbach: At HHU we are particularly concerned with process development. We take the new polymers and see how well they can be extruded with a twin-screw extruder, what the properties of the filaments are, what the release properties for the active ingredients are and how they can be influenced. We are also developing models to be able to precisely control and predict the release of active substances.
In addition, there are other issues: We are looking at the traceability of medicines in order to prevent and make it more difficult to counterfeit medicines.
In another sub-project, we are looking at how thermolabile active ingredients are degraded during the extrusion process, where the heat load is greatest, and how it can be reduced.
What are the next steps until 3D-printed medicines are ready for the market?
Quodbach: Here we have to distinguish between different application scenarios: The possibility of printing medicines directly on a doctor's prescription could become reality in the next few years with appropriate printers. One challenge will be to familiarise manufacturers with the new technology and to communicate the advantages. One advantage, apart from ensuring the quality of medicines, is that in many cases workers can be freed up for other activities.
If you think of industrial production, other perspectives arise. Because there, individual prescriptions cannot simply be produced on prescription. So far, there is no legal basis that allows for the authorisation of individually produced medicines. What is more realistic in the industrial scenario is the production of clinical trial samples for conducting clinical trials. Before a drug is approved, it goes through a rigorous testing procedure for which dosage forms with different dosages are needed. For such applications, smaller batches are usually needed, but in larger numbers. Pharmaceutical 3D printing is perfectly suited for this purpose.