INTRODUCTION:

3D printing is an "additive manufacturing" technology, where a model is created using computer-aided design software, sliced, and printed layer by layer using the layered manufacturing principle. This differs from traditional "subtractive manufacturing" techniques^1,2. Medical devices like dispersible films, microneedles, implants, transdermal patches, immediate-release and controlled-release tablets, and more have all been produced using three-dimensional printing technology^3,4. A sequence of two-dimensional layers is accumulated during the 3D printing process, creating a three-dimensional geometry. 3D printing techniques are growing in popularity because of their adaptability and the decreased cost of the required equipment. This has allowed the technologies to mature and be translated into clinical practice.

There are two primary techniques dominate 3D printing for consumer-level additive manufacturing: fused deposition modelling (FDM) and stereolithography (SLA). These processes incrementally add material, layer by layer, to construct objects. The average consumer may now purchase 3D printing, which reduces manufacturing costs and time when compared to conventional manufacturing methods^5,6. The two primary techniques utilised in consumer-level additive manufacturing for 3D printing are fused deposition modelling (FDM) and stereolithography (SLA). These processes accumulate material, layer by layer, gradually to produce objects⁷. 3D printing has significantly impacted the medical sector by enabling personalized medicinal products. 3D printing allows for customized implants, prostheses, and orthotics, leading to better patient outcomes and quality of life. Individual anatomical scans can be used to create custom-fit implants, resulting in precise fit and less problems. 3D printing has improved surgical planning and training by giving surgeons with physical representations of patient anatomy⁸.

Personalised Medicine:

The "Personalised medicine is a medical model that uses phenotypic and genotypic characterisation of individuals, such as lifestyle data, medical imaging, or molecular profiling, to tailor the right therapeutic strategy for the right person at the right time, and/or to determine the predisposition to disease and/or to deliver timely and targeted prevention," according to the Horizon 2020 Advisory Group⁹. The European Commission's Research and Innovation Unit claims that customised medicines help solve the problems of growing healthcare expenses brought on by an ageing population and more common chronic diseases, as well as the ineffectiveness of conventional medications in treating a large number of patients. In this sense, personalised medications enable the development of preventative and treatment plans that are tailored to the needs of specific patients or groups of patients, saving money on trial-and-error therapies¹⁰.

The health and safety of medications for special populations, such as the elderly and children, has long been a source of concern^11,12. Children are in a phase of growth and development, so they are especially reactive and sensitive to medication; the elderly have a reduced absorption and metabolism capacity, and the coexistence of several diseases and combination therapy is typical¹³. While current drug dosages are standardised, there are few specialised drugs for special populations, and children's medication is frequently administered by manually breaking tablets, which is not only inaccurate but also may damage the preparation's specific structure and cause adverse reactions¹⁴. Targeted distribution, controlled release, and variable dosage are examples of personalised delivery systems. Through these processes, drugs can be released in response to certain physiological cues or triggers, maximising therapeutic benefit while reducing the likelihood of adverse consequences¹⁵. There has been a sharp increase in interest in 3D printing technology because the FDA recently approved the medicine product Spritam®, which was created using 3D technology. This novel strategy has the potential to transform the creation of pharmaceutical products, especially in the area of tailored medicine¹⁶. 3D printing is revolutionising the industry by providing streamlined design and production cycles and the flexibility to transition from early development to end-product manufacture. This approach has gained traction because of its automated procedure and cost-effectiveness, outperforming conventional manufacturing techniques, particularly in on-demand production.

The substantial impact of 3D printing on personalised medicine stems from its unique capacity to provide individualised solutions, which are frequently informed by precise patient data obtained through imaging techniques such as magnetic resonance imaging (MRI) and CT scans. However, this attractive environment is not without its challenges: regulatory impediments, worries about biocompatibility, and existing technology constraints all pose obstacles. Nonetheless, continuous study and innovation in this field have the potential to solidify 3D printing's critical position in promoting personalised medical treatment.

Figure 1: 3D Printing involvement in Large Scale manufacturing

3D printing for all populations with a focus on special population:

The paediatric group appears to be the most demanding of all patients due to their specific preferences for dosage form, shape, taste, and scent. Even though the oral form seems to be the most palatable, it is difficult to fabricate and deliver to this age range. Small features like shape, colour, or taste preferences may influence a child's decision to use one dose form over another. By accommodating their unique tastes, 3DP can be of great assistance in this situation¹⁷. Giving children the right dosages based on their weight and surface area is the main issue when treating them. Rapid-dissolving tablets, Oro dispersible film formulations, and mini-pills manufactured with 3DP seem to be the best options for dispensing because swallowing is a major concern for younger children. Researchers discovered that kids preferred 4 mm-diameter mini tablets over other brands¹⁸. According to another study, ODF formulations are more appropriate for paediatric patients than oral powders in unit dose sachets¹⁹.

Additionally, giving formulations in their favourite flavour and colour can help patients adhere to their drug regimens. Chewable isoleucine tablets were developed using 3DP in a trial to treat maple syrup urine disease (MSUD). Paediatric patients accepted tablets printed in a variety of tastes (coconut, banana, lemon, etc.) and hues (light green, yellow, orange, etc.) according to their preferences. Patient acceptance is a critical component of medicine delivery, and oral tablet swallowing is challenging for paediatric patients. Additionally, FDM (Fused Deposition Modelling) was used to produce 3DP tablets for paediatric use, which have the ability to dissolve quickly. Every tablet had instant release characteristics and was destroyed in three minutes²⁰. The production of aesthetically pleasing and appetising 3DP tablets, often known as polypills, has increased the medications' adoption among paediatric patients.

Five crucial steps are involved in the sequential workflow that uses FDM 3D printing to create customised medication products from digital designs ^21,23,24. Creating a 3D digital model of the dosage form that is customised to the needs of each patient is the first step in the design phase. After that, STL format files that are compatible with the 3D printer are created from the designed 3D models. The third step entails segmenting the STL file into a layer-by-layer design, or "slicing" it for printing, and defining exact printing parameters. The feedstock material, which is needed to make the drug product, is then carefully prepared for manufacturing. The fifth and final step involves actually printing the dosage form, which is followed by a thorough evaluation procedure for ensuring both its functioning and quality²⁴.

The Evolution Of 3d Printing Technologies:

Figure 2: Illustration of Evaluation Parameters

This evolution has been supported by advances in materials, precision, and accessibility, resulting in an ever-increasing range of applications. Technology has advanced from prototyping to full-scale production, allowing for customisation and complexity that was previously considered unattainable.

Stereolithography (SLA):

Stereolithography was invented in 1986, which marked the beginning of 3D printing. This approach, which includes curing photopolymer resins with UV light layer by layer, laid the groundwork for additive manufacturing methods. One example of its early application is the fabrication of dental implants, which benefited from SLA's precision and customising capabilities ²⁵.

Figure 3: Diagramatic representation of Stereolithography

Fused Deposition Modelling (FDM):

Gained popularity because of its user-friendly methodology and compatibility with many thermoplastic materials. It specialised in developing functioning prototypes and end-use parts. For example, the aerospace industry used FDM to build lightweight components that could resist the rigours of flight.

Figure 4: Diagrammatic Operation FDM

Advancements in Personalized Medicine:

In contrast to the conventional "one size fits all" approach, personalized medicine seeks to customize pharmacological therapies for each patient by taking into account their particular physiology, medication responses, and genetic profiles. 3D printing is one of the key developing technologies causing this change. To create complex 3D items, 3D printing entails gradually layering materials under the direction of advanced computer software. Its many uses in the pharmaceutical industry include the development of medication combinations, release profiles, and dosage forms with a variety of morphologies. Personalized medicine has a lot of potential thanks to 3D printing in the pharmaceutical industry. It has the ability to modify dosage forms to meet the needs of specific patients²⁵.

· Dose personalization:

3D printing has significant potential for obtaining dose flexibility customized to individual patient needs, particularly in population groups such as paediatrics, where therapeutic doses vary depending on age and body weight. Within this perspective, the previously mentioned dosage forms can be efficiently altered utilizing 3D printing technology to deliver the precise dose required by patients. For example, in the case of orally disintegrating film (ODF) formulations, flexibility can be simply achieved by altering the amount of liquid API sprayed onto the film. Furthermore, ODFs can change shape and size to customize treatments. Similarly, dose strength can be adjusted in different dosage forms, such as pills or patches, to match unique patient needs²⁶.

· Modifying release profile:

3D printing provides a versatile way for customizing drug release characteristics to fit individual needs. One useful way is to manipulate the forms and geometries of tablets. For example, the development of immediate-release tablets for low-dose medications has demonstrated that lowering tablet thickness or creating gaps within the tablets can greatly increase drug release rates, with total release achieved in as little as 5 minutes. In another study, paracetamol tablets were shaped into various forms such as cubes, discs, spheres, pyramids, and toruses, demonstrating that the surface area-to-volume ratio could be finely adjusted to control drug release. Complex geometric shapes, such as honeycomb-shaped tablets made using 3D printing, with variations in honeycomb cell sizes, enabled for the realization of various release profiles, demonstrating the potential of dosage form geometries in influencing drug release ²⁶.

APPLICATIONS OF 3D PRINTING:

Figure 5: Diagramatic representation of medical applications of 3D printing

· Orthopaedics and prosthetics: personalized orthopaedics and bone replacements:

A new era of innovation and customisation has been brought about by the incorporation of 3D printing technology into orthopaedics and prosthetics. This innovative method makes it possible to create customized bone replacements and prosthetics that are suited to each patient’s needs. Personalized orthopaedic implants have become increasingly popular for treating challenging surgical cases in the wake of the latest advancements in software and 3D printing. 3D printing has completely changed how bone replacements are approached in orthopaedics^27,28.

· Applications in dentistry:

The biggest obstacle to general human health and wellness is now dental diseases. As 3D printing technology have advanced, they are now widely used in root canal therapy, orthodontics, and edentulous arch restoration²⁹.

· Medical devices and surgical tools:

The employment of individualized 3D models suited to specific patients’ demands has been documented Across several medical and surgical sectors. To better understand the complex and varied elements of congenital cardiac diseases, cardiology has profited from 3D models. Additionally, these models have helped in implantable device sizing for surgeries like as closing the left atrial appendage. 3D models have been essential in the field of neurosurgery for organizing surgical strategies and provide real-time direction during procedures involving intricate skull-base tumours and cerebrovascular aneurysms. In orthopaedic cases, which frequently involve hardware and reconstructions, 3D models have been used to assess anatomical components, choose the right implant sizes, and map drilling courses. Surgery for issues like scoliosis and acetabular abnormalities has benefited greatly from these models³⁰.

· Wound Dressing:

Hot melt extrusion was utilized to create the metal-homogeneously-loaded filaments, and 3D models of the ears and nose were created. The wound dressings showed bactericidal qualities and a sustained release of the various metals. It was determined that the anatomically adaptive dressings were less expensive than traditional flat dressings. In order to facilitate wound healing in vascular grafts that can support the repair of wounded vessel wound following surgical reconstruction, a 3D-printed hybrid scaffold based on (poly ethylene glycol) PEG and homogenized pericardium matrix was created³¹. When homogenized pericardium is added to PEG matrix, it alters the scaffold’s modulus and lowers the macrophages’ inflammatory signal. The resulting biomaterial was said to be extremely promising for the development of vascular grafts and for creating a new area in the reconstruction of congenital heart defects³².

ADVANTAGES OF 3D PRINTING:^30-32

· High drug loading capability compared to conventional dosage forms.

· Accurate and Precise dosing of potent drugs which are administered at small doses for activity.

· Reduced production cost due to less wastage of materials.

· Medication can be tailored to a patient in particular based on age, gender, genetic variations, ethnic differences and environment.

· Treatment can be customized to improve patient adherence in case of multi-drug therapy with multiple dosing regimen.

· As immediate and controlled release layers can be incorporated owed flexible designs, manufacturing method of dosage form and it helps in pick out the best therapeutic regimen for an individual.

· Evades batch-to-batch variations met in bulk manufacturing of conventional dosage forms.

· Manufacture of small batch is feasible and the process can be completed in a single run.

· 3D printers capture minimal space and are affordable.

DISADVANTAGES:

· Problems related to nozzle are a major challenge as stopping of the print head which affects the final products structure.

· Powder printing clogging is another hurdle.

· Possibility of modifying the final structure on to mechanical stress, storage condition adaptions and ink formulations effects.

· Printer related parameters and these effects on printing quality and printer cost ^30-32.

CONCLUSION:

In summary, a new approach in the development, production, and distribution of pharmaceuticals is represented by the use of 3D printing technology in personalized medicine. Through the development of customized drugs with controlled release, exact dosage, and unique compositions, 3D printing holds promise for improving therapeutic results, increasing patient adherence, and lowering medical expenses. The current regulatory, technological, and financial obstacles must be overcome as this sector develops in order to guarantee the broad use of 3D printing in customized medicine, which will ultimately revolutionize healthcare in the future.

REFERENCES:

1. Bethany C.G, Jayda L.E, Sarah Y.L, Chengpeng C, Dana M.S. Evaluation of 3D Printing and Its Potential Impact on Biotechnology and the Chemical Sciences. Anal. Chem. 2014, 86, 3240–3253.

2. Ishita M, Gurvinder K, Amir S, Aneesah, M.; Cato, T.L. Progress in 3D Bioprinting Technology for Tissue/Organ Regenerative Engineering. Biomaterials. 2020; 226: 119536.

3. Jimenez M, Romero L, Dominguez I A, del Mar Espinosa M, Domínguez M. Additive Manufacturing Technologies: An Overview about 3D Printing Methods and Future Prospects. Complexity. 2019; 2019: 1–30.

4. Holzmann P, Breitenecker RJ, Soomro AA, Schwarz EJ. User entrepreneur business models in 3D printing. J ManufTechnolManag. 2017; 28:75–94.

5. Computer Sciences Corporation. 3D printing and the future of manufacturing. Tysons (VA): The Corporation; 2012.

6. Konta A, Garcia-Pina M, Serrano D. Personalised 3D Printed Medicines: Which Techniques and Polymers Are More Successful Bioengineering. 2017; 4: 79.

7. Nguyen V.V.T, Ye S, Gkouzioti V, van Wolferen M.E, Yengej F.Y et al. A human kidney and liver organoid-based multi-organ-on-a-chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell-derived extracellular vesicles. J. Extracell. Vesicles. 2022; 11: e12280.

8. European Commission Personalised Medicines. Available online: https://research-and-innovation.ec.europa.eu/research-area/health/personalised-medicine_en (accessed on 9 November 2022).

9. Nimmesgern E, Norstedt I, Draghia-Akli R. Enabling personalized medicine in Europe by the European Commission’s funding activities. Pers Med. 2017; 14: 355–365.

10. Don W, Lauren B, Kelly C. A chieving high dose drug load with rapid dispersion using 3D printing. ApreciaZipdose. 2014.

11. Alhnan MA, Okwuosa TC, Sadia M, Wan KW, Ahmed W, Arafat B. Emergence of 3D printed dosage forms: Opportunities and challenges. Pharm Res. 2016;33(8):1817-32.

12. Giangreco NP, Elias JE, Tatonetti NP. No Population Left behind: Improving Paediatric Drug Safety Using Informatics and Systems Biology. Br J Clin Pharmacol. 2022; 88: 464–1470.

13. Shibata Y, Itoh H, Matsuo H, Nakajima K. Differences in Pharmaceutical Intervention Triggers for the Optimization of Medication by Patient Age: A University Hospital Study. Biol Pharm Bull. 2021; 44: 1060–1066.

14. Aho J, Bøtker JP, Genina N, Edinger M, Arnfast L, Rantanen J. Roadmap to 3D-printed oral pharmaceutical dosage forms: feedstock filament properties and characterization for fused deposition modeling. J Pharm Sci. 2019; 108:26–35.

15. Jamroz W, Szafraniec J, Kurek M, Jachowicz R. 3D printing in pharmaceutical and medical applications – recent achievements and challenges. Pharm Res. 2018; 35:176.

16. M. Preis, H. Oblom 3D-Printed drugs for children are we ready yet? AAPS PharmSciTech. 2017; 18 (2): 303-308.

17. DA. VanRietNales, BJ deNeef, AF. Schobben, JA. Ferreira, TCG Egberts, CMA Rademaker Acceptability of different oral formulations in infants and preschool children. Archives of Disease in Childhood. 2013; 98 (9):725-731.

18. H. oblom, E. Sjoholm, M. Rautamo, N. Sandler Towards printed pediatric medicines in hospital pharmacies: comparison of 2D and 3D-printed orodispersible warfarin films with conventional oral powders in unit dose sachets. Pharmaceutics. 2019; 11 (7): 334.

19. A Goyanes, CM. Madla A, Umerji G. DuranPineiro JM. Giraldez Montero MJ. Lamas Diaz 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.

20. DG. Yu, XX. Shen C. LM Zhu K. White XL Yang. Novel oral fast-disintegrating drug delivery devices with predefined inner structure fabricated by Three-Dimensional Printing. J Pharm Pharmacol. 2009; 61 (3): 323-329.

21. HG. Yi, YJ. Choi KS. Kang. et al. A 3D-printed local drug delivery patch for pancreatic cancer growth suppression J Contr Release. 2016; 238: 231-241.

22. PR. Martinez, A. Goyanes, AW. Basit S. Gaisford Fabrication of drug-loaded hydrogels with stereolithographic 3D printing. Int J Pharm. 2017; 532 (1): 313-317.

23. N. Genina, J. Hollander, H. Jukarainen, E. Makila, J. Salonen, N. Sandler Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices.

24. Hull CW. Apparatus for Production of Three-Dimensional Objects by Stereolithography. U.S. Patent 4575330, 1986.

25. Vaz VM, Kumar L. 3D printing as a promising tool in personalized medicine. AAPS PharmSciTech.2021;22:49.96.

26. Cummings D. Prosthetics in the developing world: a review of the literature. Prosthet Orthot Int.1996; 20:51–60.

27. Barcik J, Ernst M, Schwyn R, Freitag L, Dlaska CE, Drenchev L, et al. Development of surgical tools and Procedures for experimental preclinical surgery using computer simulations and 3D printing. Int JOnline Biomed Eng. 2020; 16:183–95

28. Rittel D, Shemtov-Yona K, Lapovok R. Random spectrum fatigue performance of severely plastically Deformed titanium for implant dentistry applications. J MechBehav Biomed Mater. 2018; 83:94–101.

29. Schlegel L, Ho M, Fields JM, Backlund E, Pugliese R, Shine KM. Standardizing evaluation of patient specific 3D printed models in surgical planning: development of a cross-disciplinary survey tool for Physician and trainee feedback. BMC Med Educ. 2022; 22:614.

30. Bracaglia LG, Messina MJ, Winston S, Kuo C-Y, LermanM, Fisher JP. Printed pericardium hydrogels to promote wound healing in vascular applications. Biomacromolecules. 2017;18(11):3802–11.

31. Awad A, Fina F, Trenfield SJ, Patel P, Goyanes A, Gaisford S, et al. 3D printed pellets (miniprintlets): a novel, multi-drug, controlled release platform technology. Pharmaceutics. 2019; 11:148.

32. Pelkonen O. Metabolism and Pharmacokinetics in Children and the Elderly. Expert Opin. Drug Metab. Toxicol. 2007; 3: 147–148.

33. Pratico AD, Longo L, Mansueto S, Gozzo L, Barberi I. et al. Off-Label Use of Drugs and Adverse Drug Reactions in Pediatric Units: A Prospective, Multicenter Study. Curr Drug Saf. 2018; 13: 200–207.

Received on 11.02.2025 Revised on 28.02.2025

Accepted on 15.03.2025 Published on 09.05.2025

Available online from May 12, 2025

Res. J. Pharma. Dosage Forms and Tech.2025; 17(2):137-142.

DOI: 10.52711/0975-4377.2025.00020

This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License. Creative Commons License.