Three-dimensional printing (3D printing) is gaining popularity in different areas from manufacturing to medicine. It is believed to be considered the beginning of the new industrial revolution. Not surprising 3D printing is also gaining popularity in drug development although its potential is not fully discovered. Currently 3D printing is explored as a potential method for producing solid oral dosage forms (like tablets and capsules) and its role in developing personalised medicines. However, like all new technologies 3D printing has its advantages and challenges.
What types of 3D printing technologies are used?
- Vat photopolymerisation is a process that utilises a light source (e.g., laser) to selectively cure a vat of liquid photopolymer, transforming it into a solid object. Examples of such are stereolithography (SLA), digital light processing (DLP), and continuous liquid interface production (CLIP) technologies;
- Binder jetting (BJ) revolves around the selective binding of solid powder particles by spraying a liquid agent;
- Powder bed fusion is a selective thermal process that involves the fusion of powder particles by the application of a laser or other heat source. It includes selective laser sintering (SLS), multijet fusion (MJF), direct metal laser sintering/selective laser melting (DMLS/SLM), and electron beam melting (EBM);
- Material jetting is a selective technique in which liquid droplets of materials are deposited on a surface. These droplets spontaneously solidify [known as drop-on-demand (DOD)] or can be cured or fused using an ultraviolet (UV) light [known as material jetting (MJ)] or a heat source [known as nanoparticle jetting (NPJ)]; 5
- Direct energy deposition is a process that selectively deposits a form of focused thermal energy (e.g., laser) directly onto powder particles, causing them to melt and fuse. It involves two technologies; laser engineering net shape (LENS) and electron beam additive manufacturing (EBAM);
- Sheet lamination; compromises the bonding of materials in the form of sheets (e.g., cut paper, plastic or metal) to fabricate 3D objects. It is often known as laminated object manufacturing (LOM) or ultrasonic additive manufacturing (UAM);
- Material extrusion is a technology that involves the selective dispensing of material in a semisolid form. This technology is further subdivided into fused deposition modelling (FDM), which utilises thermoplastics, and semisolid extrusion (SSE), which utilises gels and pastes.
Advantages of 3D printing in drug development
- Drug research is an extensive and expensive process, which requires sophisticated supply chain. 3D printing can reduce the costs of clinical research phase by allowing producing small or ‘one-off’ batches of formulations or drugs. This is especially important in early stage – in drug discovery, pre-clinical studies and first in human (FIH) studies. For example, chemists from University of Glasgow have produced successfully ibuprofen. Another team has synthetized baclofen.
- This method could be very successful in producing different molecules on a small scale which normally have high cost or poor stability.
- 3D printing could also enable producing drugs on a small scale in remote locations, which otherwise will not support the process.
- 3D printing was used in pre-clinical drug discovery by producing 3D print of animal and human tissues, which allows these tissues to be used in studying drug toxicity and metabolism. For example, team from Harvard University was able to 3D print the first cardiac microphysiological device. Also there are number of organs that have been 3D printed like stomach, pancreas and small intestine, which gives new opportunities for in vitro drug testing and reduce the number of animal models.
- 3D printing could speed up the drug manufacturing process on a small scale.
- 3D printing does not require serious modifications and major labour input.
- 3D printing is fast – it could take average of 6.5 min to produce a small object which will take 3.5 up to 11.5 hours with conventional methods.
Challenges in 3D printing
- The biggest challenge is the high price of the 3D printer, which could vary from £1500 to £4 million.
- Another big issue is potential toxicity due to presence of unreacted monomers.
- The final product of the 3D printing has low mechanical properties – low friability and hardness values.
- Another potential risk is drug degradation during the 3D process because of the high temperatures that are used during printing.
While current 3D printing technologies have their limitations it is still early phase of development and probably in the future some of these challenges will be overcame. 3D printing is definitely existed field which has its potential application in drug development.
Published on 1 March 2019
Author: Olga Peycheva, Director at Solutions OP Ltd. Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe