The aging population and the daily increase in the number of chronic diseases, results in the increasing consumption of multiple pills by patients, at different times throughout the day. The major challenge that occurs is taking the right medicines at the right time, particularly for dementia and other similar conditions; currently, polypills are used to treat some chronic diseases. A polypill is a medication available in a pill form (i.e., tablet or capsule), consisting of two or more active pharmaceutical ingredients. They are affordable, multiple-target, fixed-combinations, and easy to produce in large quantities; however, one disadvantage is that they don’t always help all patients.
Therefore opportunities for 3D printed drugs arise. These are personalized medicines and can be produced in small batches with carefully tailored sizes, shapes, dosage forms, and drug release properties according to the needs of different patients. This could radically change the future treatment landscape of multiple diseases. The 3D printing technology also allows masking the taste of the pharmaceutical ingredient by adding flavor into the pill itself without the need for film coating. 3D printing technology has also previously been used to develop bioprinted organs, prosthetics, and implants, so the precedent exists for exploration of its applications in pill printing.
3D printers can be easily installed in hospitals, clinics, pharmacies, and any remote location which enables the lean management of raw materials. 3D printing is also a smart new way of producing those drugs that require cold chain storage at a reduced cost, less waste, and lower environmental burden, by using exact amounts of API.
3D printing in healthcare
According to the 2021 forecast publication (link), the 3D printed drug industry will grow significantly to reach US$ 2,064.8 million at a compound annual growth rate of 15.2% (forecast period 2021-2027). Besides the prevalence rate of chronic diseases (which continuously increases) another emerging trend, that of dysphagia boosts the need for 3D printed, customized to the needs of each patient, drugs. The prevalence rate of dysphagia in the general population (29-32 years) is around 16-23% which increases to 27% in the geriatric population of over 76 years of age. According to a report by the United Nations, the projected number of older people will be approximately 1.5 billion in 2050, so the dysphagia issue will likely keep increasing.
3D printed drugs
In 2015, Aprecia pharmaceuticals launched the first 3D-printed FDA-approved drug named Spritam (levetiracetam) to treat epilepsy. The drug is produced by ZipDose technology. Spritam is an orodispersible tablet that disintegrates within a second when in contact with liquid. Additionally, very high doses can be administered (up to 1,000 mg) which are not typically achievable by current methods.
T19 by Triastek is another 3D printed drug that received investigational new drug clearance from the US FDA for the treatment of rheumatoid arthritis. Triastek has plans to file in H2 2021 followed by applications in Europe and Japan.
The current 3D-drug printing technologies in the market
- Fused Deposition Modeling: This technology-based melt extrusion method is used to deposit filaments loaded with active ingredients for the manufacturing of the pill. The major challenge with this technology is to adjust extrusion temperature with the stability of the active ingredients
- Direct Powder Extrusion: This technique is patented by FabRX, mainly used to develop high load medication with a high disintegration rate due to the porosity of the material. The technology enables the production of sustained-release drugs
- Stereolithography: It is the process by which the liquid converts into solid objects. The active ingredients are included in the polymer network which is shaped into pills
- Selective Laser Sintering: The process of using the power of laser technology to sinter the small particles of polymer powder into a solid structure based on a 3D model. The technique allows the development of controlled release or orodispersible pills
- Inkjet printing: The active ingredients and excipients sprayed through a nozzle create a layer-by-layer polymer structure that gets solidified with the help of a powder substrate.
In addition to the technologies mentioned above, many pharmaceutical companies are developing their own technologies. For example, UK-based FabRX developed M3DIMAKER, Merck KGaA has collaborated with AMCM for the development and production of 3D printed pharmaceuticals and GlaxoSmithKline also has a partnership with the University of Nottingham to produce 3D printed ropinirole tablets for the treatment of Parkinson’s disease.
Drivers of 3D-drug printing
Increased product complexity:
- Manufacturing: easy to produce complex drugs with the same cost and speed as a simpler drug
- No assembly required and 3D printing may enable simpler manufacturing of combination products
- Combination of multiple APIs into one dosage form
- Unlimited design options enable the creation of a new product that may not have previously been possible to manufacture
Increased personalization:
- Precision drug design may allow for the creation of drugs that are a “match” for a patient’s physiology and anatomy
- Lower production volumes are possible by enabling personalization and smart use of APIs
- Lean manufacturing allows for the generation of the smallest number of doses required for a specific treatment course
Point of care manufacturing and process scale-up:
- Almost zero lead time, which reduces the need for complex supply chain and storage
- Compact and portable 3D-printing devices, enable to manufacture a product at the hospital, clinic, or at any remote location.
- Low- / zero-skill manufacturing requirements when using 3D printers with preloaded drug designs
Regulatory gaps and challenges
- Despite having unique advantages, 3D-printed drugs come with some drawbacks. The current regulatory structure only provides some guidance for the mass production of drugs using 3D printing technology. However, there are no regulations available for on-demand manufacturing at hospitals, clinics, or any other remote location.
- The complete knowledge about supply chain, shelf life, dispensing properties, dose manufacturing, or administration at home for 3D-printed drugs are still not well understood
- There are issues relating to the potential device-originating safety hazards, due to the volatile nature of printing materials during the manufacturing process, particularly when operations are performed outside of a conventional manufacturing facility
- Currently, no legislation exists to protect the intellectual property behind 3D printed drugs
Conclusion
The 3D-printed drugs have the potential to change the future of conventional medicines by providing more specific and personalized treatment for patients. The most burning issue is the question of regulation and drug delivery. However, a breakthrough might be just around the corner as many pharmaceutical companies have started to invest in 3D-printed drug technology.
#3Dprinting #personalizedmedicine #drugdesign #drugdelivery
Sources:
https://www.fda.gov/media/125479/download
https://www.3dnatives.com/en/3d-printed-drugs-personalized-medicine-140520204/
https://drug-dev.com/3d-printing-3d-printed-drugs-hold-great-potential-for-personalized-medicine/