Supporting the successful compounding of drugs with 3D printing processes has the potential to not only fulfil unmet patient needs but also drive efficiencies in hospital pharmacies. Ian Soulairol from the Institut Charles Gerhardt Montpellier at Montpellier University and pharmacist at the Department of Pharmacy of Nîmes University Hospital in France shares insights into how this technology is evolving and what it means for clinical practice now and in the future.
3D printing, or additive manufacturing, is based on the superimposition of layers of material to produce an object according to a design previously modelled by computer-aided design software.1 This manufacturing technology is becoming increasingly important in all production sectors after having been first commercialised in the mid-1980s.
Since then, several different methods of 3D printing have been developed, and many of these are now used for pharmaceutical purposes.2 The main types used in this industry are binder jet printing, fused deposition modelling, semi-solid extrusion, direct powder extrusion, stereolithography and laser sintering.2
Generally, these printing technologies follow standard processes to produce the printed drug – known as the printlet. These are:
- Design – designing the formulation (including the relevant shape and size) and transferring the blueprint to the relevant 3D printer
- Development – the printlet ‘ink’, which comprises the selected drug and the relevant excipient(s), is loaded into the printer and the parameters are selected. These include printing time, temperature, etc., and are based on the characteristics of the drug and the type of printer
- Dispensing – the printer then prepares the printlet in a layer-by-layer manner.2
The first drug produced through printing technology based on inkjet on powder was approved by the US FDA in 2015.3 But what about 3D drug printing in hospitals?
3D printing potential in hospital pharmacy
Hospital pharmacies manufacture medicines for which the pharmaceutical industry is not able to offer a ‘standard’ solution, particularly for paediatric indications. These products require a high degree of adaptability, particularly in terms of dosage, to meet patients’ needs. For oral drugs, this usually involves small manual production runs to produce hard capsules or liquid formulations.
The use of 3D printing techniques could provide a solution to this need, as they combine the advantages of dry oral forms with the much-desired flexibility of liquid forms. To achieve this flexibility, 3D printing needs to be at the point of care, and extrusion techniques (hot or semi-solid) are the most suitable for outsourcing production compared with techniques such as laser powder sintering, as they require little or no post-printing treatment.
Among extrusion printing techniques, fused deposition modelling (molten filament deposition) printing is currently the most widely used in research for printing medicines. Printing is carried out via a filament composed of thermoplastic polymers and the active ingredient(s).
This filament is melted at a specific temperature and extruded through a nozzle at the print head, which moves to deposit successive layers to form the printlet.4
This technology is not the easiest to use. It requires mastery of the formulation and manufacture of the filament, and also of the physical parameters – such as the diameter of the thread – which must be as regular as possible. In addition, the mechanical properties must be fully controlled if printing is to be successful.
This complexity might explain why, to date, despite many scientific publications on the subject, few clinical studies have been published on the subject. However, once developed, this technology could greatly aid the delivery of personalised medicines.
Another extrusion technique is semi-solid extrusion (SSE). 3D printing using SSE, also known as pressure-assisted microsyringe printing, involves extruding a semi-solid material using a mechanical, pneumatic or solenoid piston.5 Easier to use than filament fusion, it also has the advantage of being able to work at room- or lower temperatures.
These are the two main printing techniques currently being considered to produce medicines in hospitals, and SSE is the first technique to have enabled a paediatric clinical trial using impressions made in a hospital.6
Wide-reaching benefits of 3D printing
One of the main advantages of 3D printing in hospital pharmacies is personalising care for the patient. Industrial pharmaceutical manufacturing often relies on the mass production of standardised medications, resulting in a one-size-fits-all approach. Unsuitable for large-scale production, 3D printing focuses on patient-specific production, allowing pharmacists to tailor medications to specific conditions.
For patients requiring atypical dosages, or for those with dysphagia who are unable to swallow ‘standard’ pills, the customisation that 3D printing enables not only improves treatment effectiveness but also enhances treatment acceptability and adherence.
Additionally, this technology offers great design flexibility, allowing healthcare professionals to create solutions tailored to specific needs in the form of single and varying dosages.
Overdosing or underdosing risks are common in children who lack access to personalised treatments, and, in paediatric and geriatric services in particular, the advantage of this flexibility facilitates treatment adherence while ensuring patient safety.
3D printing can also accelerate the manufacturing process, reducing operator time and allowing significant flexibility. Indeed, automating the manufacturing process results in faster handling and a more customised response. So, with just one click, pharmacists can print tailored oral formulations safely and swiftly.
Moreover, hospital pharmacies often encounter challenges related to drug shortages. In the event of disruptions to the pharmaceutical supply chain, 3D printing can provide a reliable solution. By enabling on-site production, hospitals can reduce dependence on external suppliers and ensure an efficient and timely supply of essential medications.
The adaptability of 3D printing allows for a rapid response to varying demands, mitigating the impact of shortages on patient care. Furthermore, the technology offers flexibility in adjusting production according to specific hospital needs, optimising resources and reducing waste.
From translational to clinical research
Between 2015 and 2023, very few human trials were described. One of the first trials was carried out in 2017 and assessed the acceptability of printed medicines in an open-label, randomised, exploratory pilot study of 50 participants.7
Goyanes et al investigated the influence of the shape, size and colour of different placebo 3D-printed tablets manufactured by fused deposition modelling on end-user acceptability regarding picking and swallowing.
Colour and geometry both influenced the perception of the end-user. Spherical forms were least liked and smaller sizes were preferable, although the perception of size was also influenced by the shape of the tablet.7
This trial was followed in 2019 by the first evaluation of the use of 3D printing of medications in a hospital. The Spanish researchers evaluated the safety and acceptability of SSE-printed isoleucine formulations in the treatment of maple syrup disease in children. They showed that 3D printing is an effective way of preparing oral tailored-dose therapies.6
The single-centre, prospective crossover experimental study evaluated isoleucine blood levels after six months of treatment with capsules prepared by manual compounding and personalised chewable printlets.6
Isoleucine blood levels were well controlled using both types of formulation. However, the printlets showed mean levels closer to the target value, as well as less variability. The 3D printed formulations were also well accepted by patients regarding their flavour and colour.
The results of a bioequivalence study of printed sildenafil in 12 healthy volunteers carried out at Leiden Medical Center in the Netherlands were published in 2023.8
The manufacturing process gave reproducible 3D-printed tablets that adhered to quality control requirements. The 90% confidence intervals of both AUC0-t and Cmax ratios were within bioequivalence limits and showed that the printed tablet formulation at the point of care was bioequivalent to its marketed originator.8
Conclusion
Personalised medicine is currently hindered by the paucity of flexible drug formulations and manual compounding of tailored drug formulations by pharmacists – particularly in paediatrics – is required.
3D printing allows a transition from traditional large-scale manufacture to small-scale production at the point of care, which can fulfil unmet clinical needs. The potential benefits that 3D printing offers on cost-effectiveness and expediting swift delivery of medicines for clinical practice and patients are evident.
Today, 3D printers are starting to arrive in hospital pharmacies, resulting in a significant increase in the use and integration of this technology in the healthcare setting.
Author
Ian Soulairol PharmD PhD
Institut Charles Gerhardt Montpellier (ICGM), Montpellier University, France; pharmacist at the Department of Pharmacy of Nîmes University Hospital in France
References
- Seoane-Viaño I et al. Translating 3D printed pharmaceuticals: From hype to real-world clinical applications. Adv Drug Deliv Rev 2021;174:553–75
- Basit A, Trenfield S. 3D printing of pharmaceuticals and the role of pharmacy. Pharm J 2022
- FDA approves the first 3D printed drug product. www.multivu.com/players/English/7577251-aprecia-pharmaceuticals-spritam/ (accessed March 2024)
- Awad A. 3D printed medicines: A new branch of digital healthcare. Int J Pharm 2018;548:586–96
- Vaz VM, Kumar L. 3D Printing as a Promising Tool in Personalized Medicine. AAPS PharmSciTech 2021;22:49
- Goyanes A et al. Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: First single-centre, prospective, crossover study in patients. Int J Pharm 2019;567:118497
- Goyanes A et al. Patient acceptability of 3D printed medicines. Int J Pharm 2017;530:71–8
- Lyousoufi M et al. Development and Bioequivalence of 3D-Printed Medication at the Point-of-Care: Bridging the Gap Toward Personalized Medicine. Clin Pharmacol Ther 2023;113:1125–31.
