An Overview of the 3D Printing in Personalized Medicine and Its Application

Fig. 1 Binder Jetting (BJ-3DP)

Fig.2 Fused deposition modelling

Fig.3 Semi-Solid extrusion

Fig. 4 Selective Laser sintering

Fig.5 Stereolithography and digital light processing

Fig. 6 Inkjet Printing

Advantages:

• Extremely precise for low-dose potent drugs
• Suitable for orodispersible films and wafers
• No heat required

Limitations:

• Limited viscosity range
• Not suitable for high-dose formulationsRelies on solvent evaporation

Inkjet printing is widely explored for pediatric dosing and personalized thin films [13,39].

2.7 Emerging Hybrid and Advanced Technologies

Emerging techniques combine multiple 3D printing processes to improve functionality:

• 4D printing: structures respond to stimuli like pH, heat, or moisture [22]
• Bioprinting: printing living cells and biomaterials for regenerative medicine [23]
• Hybrid printers: combining FDM + SSE or SLA + inkjet for multi-material polypills [40]

These innovations represent the next phase of personalized drug design and delivery.

 3. Applications of 3D Printing in Personalized Medicine

The shift toward individualized therapies has increased the demand for flexible, adaptable, and patient-specific dosage forms. Three-dimensional (3D) printing enables such personalization by allowing modifications in dose, shape, porosity, surface architecture, release kinetics, and drug combinations [41]. Unlike conventional manufacturing, 3D printing supports rapid prototyping and on-demand production, making it particularly suitable for populations requiring customized drug delivery systems [42].

Below are the major clinical applications of 3D printing in personalized medicine.

3.1 Pediatric Personalized Dosage Forms

Children often require precise dose adjustments due to developmental differences in pharmacokinetics and pharmacodynamics. Standard tablets may be inappropriate due to swallowing difficulties, dose inflexibility, and poor palatability [43].

3D printing enables:

• Accurate mg-level dose adjustments
• Orodispersible tablets with enhanced mouthfeel
• Patient-friendly shapes (animals, stars)
• Flavoring and color customization

Flexible combinations of multiple drugsSemi-solid extrusion (SSE) and inkjet printing are especially suitable because they operate at low temperatures and accommodate thermolabile pediatric medications [44]. Clinical studies have demonstrated the feasibility of hospital-based pediatric dosing using 3D printing [45].

3.2 Geriatric and Special Populations

Elderly patients commonly face polypharmacy, dysphagia, cognitive decline, and variable organ function. Traditional dosage forms may not adequately meet their personalized needs [46].

3D printing offers:

• Tablets optimized for swallowing (reduced density or modified shape)
• Larger, textured surfaces for ease of handling
• Personalized dose strengths for renal/hepatic impairment
• Custom release profiles to maintain stable plasma levels

Additionally, FDM enables compartmentalized structures that isolate incompatible drugs—valuable for geriatric polypharmacy [47].

3.3 Polypharmacy and Polypills

Polypharmacy increases the risk of medication errors, non-adherence, and drug interactions. Conventional fixed-dose combinations have limited flexibility. 3D printing can create multi-compartment polypills where each drug is placed in a separate region with tailored release profiles [48].

Benefits include:

• Reduced pill burden
• Personalized drug combinations
• Improved adherence
• Customizable dosing ratios
• Possibility to sequence release (immediate + sustained in one pill)

Khaled et al. successfully fabricated 3D-printed polypills containing up to five drugs using FDM [49].

3.4 Controlled-Release and Zero-Order Release Systems

3D printing enables unprecedented control over internal geometry, which directly enables tailoring drug release kinetics [50].

Controlled-release approaches achievable via 3D printing:

• Zero-order release through channel-like structures
• Biphasic and pulsatile release
• Gastroretentive systems with hollow or floating geometries
• Delayed-release systems via coated or multi-material layers

FDM’s ability to program infill density, shell thickness, and internal compartmentalization makes it highly suitable for sustained-release dosage forms [51].

3.5 Implants and Tissue Engineering

Additive manufacturing allows the development of patient-specific implants guided by medical imaging (CT, MRI). Implants can be loaded with drugs for localized, site-specific therapy [52].

Applications include:

• Bone implants matching patient anatomy
• Biodegradable polymer implants delivering chemotherapy
• Tissue-engineering scaffolds for regeneration
• High-resolution microneedle patches using SLA/DLP
• Bioprinting enables printing living cells and bioinks to create viable tissues [53].

3.6 Oncology Applications

Cancer therapy demands exceptionally precise dosing and combination strategies. 3D printing supports personalized oncology by enabling:

• Custom chemotherapeutic dosing based on pharmacogenomics
• Implantable drug depots that slowly release chemotherapeutic agents
• 3D tumor models for personalized drug screening
• Patient-specific polypills for complex treatment regimens [54]

Implantable PLA or PCL-based depots have shown promise for sustained intratumoral delivery, reducing systemic toxicity [55].

3.7 Point-of-Care (POC) Manufacturing

Point-of-care 3D printing allows onsite production of patient-specific medicines in hospitals or pharmacies [56].

Benefits include:

• Rapid response to dose adjustments
• On-demand solutions for shortages
• Personalized formulations for rare diseases
• Lower cost and reduced waste

Semi-solid extrusion (SSE) is the most practical technique for POC compounding due to minimal setup, safe operating temperature, and compatibility with various APIs [57].

4. Advantages of 3D Printing in Personalized Medicine

Three-dimensional (3D) printing offers multiple advantages over conventional pharmaceutical manufacturing, particularly for personalized therapy. These benefits arise from the digital, layer-by-layer fabrication process, which allows an unprecedented degree of control over critical quality attributes such as dose, geometry, porosity, and release profile [58,59].

4.1 Precise Dose Personalization

One of the most significant advantages is the ability to precisely tailor the dose for individual patients by modifying digital design parameters such as infill density, tablet size, or thickness [60]. This is particularly important for:

• Pediatric weight-based dosing
• Geriatric patients with organ impairment
• Drugs with a narrow therapeutic index (NTI)
• Oncology medications requiring individualized regimens

3D printing allows milligram-level dose titration without the inaccuracies associated with tablet splitting or manual compounding [61].

4.2 Customizable Drug Release Profiles

Traditional dosage forms rely heavily on coating and matrix technologies to control release, which limit design complexity. In contrast, 3D printing can modify:

• Internal channel networks
• Shell thickness
• Infill percentage
• Multi-layer configurations

These features enable immediate, sustained, delayed, pulsatile, and zero-order release profiles from a single design platform [62,63]. FDM-printed tablets have demonstrated near zero-order release kinetics through geometry-driven design [64].

4.3 Complex Geometries and Internal Architectures

Additive manufacturing is not restricted to simple biconvex tablet shapes. It can create:

• Hollow structures
• Honeycomb matrices
• Multi-compartment “core–shell” designs
• Floating systems with air-filled cavities

These geometries influence both mechanical strength and drug release behavior and cannot be achieved easily using conventional compression-based manufacturing [65].

4.4 Multi-Drug Polypills and Reduced Pill Burden

3D printing enables integration of several APIs into a single polypill while keeping them physically separated in different compartments [48,49,66]. This allows:

• Customized multi-drug regimens
• Reduced pill burden in chronic diseases
• Minimization of administration errors
• Individual adjustment of each component’s dose and release behavior

Such polypills are especially beneficial for elderly patients and those with multiple chronic conditions [67].

4.5 On-Demand and Decentralized Manufacturing

Because 3D printing relies on digital design files rather than physical tooling, dosage forms can be manufactured:

• On demand
• In small batches
• At or near the point of care

This reduces the need for large inventories, shortens supply chains, and offers flexibility in responding to patient-specific dosing needs or drug shortages [42,56,68]. Hospital-based printing has already been demonstrated for personalized pediatric formulations [45].

4.6 Improved Patient Acceptability and Adherence

Patient-centric dosage form design is facilitated by:

• Child-friendly shapes and colors
• Orodispersible or fast-dissolving structures
• Texture and size optimized for swallowing
• Visual differentiation between formulations

Studies have shown that children prefer colorful, uniquely shaped 3D-printed tablets over conventional formulations [44,69]. Improved acceptability is expected to enhance adherence, particularly in pediatrics and geriatrics [70].

4.7 Rapid Prototyping and Shorter Development Cycles

3D printing eliminates the need for multiple sets of punches, dies, and molds. Formulation scientists can iterate designs rapidly by modifying CAD models and reprinting [71]. This accelerates:

• Preclinical screening
• Design of experiment (DoE) studies
• Optimization of release characteristics
• Formulation selection prior to scale-up

As a result, development time and cost can be significantly reduced [72].

4.8 Reduced Material Waste and Efficient Use of APIs

Because material is deposited only where needed, waste is minimized compared with subtractive or compression-based methods [25]. This is particularly advantageous for:

Costly biologicals

Highly potent small molecules

Drugs available only in limited quantities

Powder recycling can further increase material efficiency in SLS and BJ-3DP processes [73].

4.9 Seamless Digital Integration

3D printing is inherently compatible with digital health technologies, including:

• Electronic health records (EHRs)
• Computerized physician order entry (CPOE)
• Clinical decision support systems
• AI-driven dosing algorithms

These links make it possible to generate “digital prescriptions” that are automatically translated into printable dosage forms [74].

5. Limitations and Challenges

Despite its transformative potential, 3D printing in pharmaceuticals faces several scientific, technological, regulatory, and economic challenges. These limitations must be addressed before routine clinical and industrial adoption becomes feasible [75]. The primary challenges are summarized below.

5.1 Regulatory and Quality Assurance Challenges

Additive manufacturing introduces new variables—including digital workflow control, software versions, printer calibration, layer resolution, and post-processing steps—that complicate regulatory assessment and quality standardization [76].

Key regulatory challenges include:

• Lack of specific GMP guidelines for 3D-printed drug products
• Variability introduced by hardware differences (printers, nozzles, lasers)
• Limited pharmacopeial standards for printed formulations
• Defining acceptable in-process controls
• Digital file security and version traceability

Although the FDA, EMA, and other agencies have published guidances related to additive manufacturing, a unified regulatory framework for pharmaceutical 3D printing is still emerging [77,78].

5.2 Limited Availability of Pharmaceutical-Grade Printable Materials

Many materials compatible with industrial additive manufacturing (e.g., PLA, ABS) are not approved for pharmaceutical use. Conversely, pharmaceutically acceptable excipients may lack the mechanical and thermal properties required for printing [79].

Challenges include:

• Few GRAS polymers suitable for FDM and SLS
• Limited biocompatible photopolymers for SLA/DLP
• Stability concerns with UV-curable resins
• Insufficient data on extractables/leachables from printed devices

Research continues on novel printable excipients, bioinks, and composite materials, but commercial availability is still limited [80].

5.3 Thermal and Mechanical Constraints

Technologies such as FDM and SLS use elevated temperatures that may degrade thermolabile drugs [81]. Even at lower temperatures, rapid heating and cooling cycles can induce polymorphic transformations or alter drug crystallinity [82].

Mechanical issues include:

• Poor layer adhesion
• Weak mechanical strength in porous BJ-3DP structures
• Fragility in rapidly disintegrating tablets
• Cracking or warping during cooling

These issues affect product robustness, transportability, and shelf-life.

5.4 Stability Concerns

Ensuring long-term stability of 3D-printed dosage forms remains a major challenge. Factors affecting stability include:

• Moisture absorption (especially in SSE formulations)
• Residual solvents in inkjet or SSE systems
• Residual photoinitiators in SLA/DLP products
• Temperature-driven degradation during printing or storage [83]

Few studies have conducted full ICH (Q1A) stability testing on printed dosage forms [84].

5.5 Scale-Up Limitations

Most 3D printing systems are optimized for prototyping, not mass production. Scaling up presents difficulties such as:

• Long printing times for batch quantities
• High equipment costs
• Printer-to-printer variability
• Limited throughput in POC environments [85]

For industrial mass production, hybrid workflows combining traditional manufacturing and additive techniques may be required [86].

5.6 Quality Control (QC) and Reproducibility Issues

3D-printed dosage forms can exhibit significant batch-to-batch variability depending on printer calibration, ambient conditions, and material quality [87].

QC challenges include:

• Ensuring uniform drug distribution within filaments or gels
• Monitoring internal structure (requires micro-CT, Raman, NIR imaging)
• Establishing in-process PAT tools
• Validating digital workflows, slicer settings, and print paths

Additive manufacturing requires a more extensive QC approach than conventional tablet manufacturing [88].

5.7 Need for Post-Processing Steps

Post-printing steps such as drying, UV curing, support removal, sterilization, or sintering add complexity and increase overall production time [89]. These steps may also alter mechanical strength, drug content uniformity, or surface morphology.

5.8 Safety and Toxicological Concerns

Safety concerns arise from:

• Residual unreacted monomers in SLA/DLP products [90]
• Potential leachables from printer parts
• Toxic by-products formed at high temperatures
• Photoinitiator migration
• Comprehensive toxicological data for printed oral pharmaceuticals remain limited.

5.9 Lack of Skilled Personnel and Infrastructure

Successful adoption of pharmaceutical 3D printing requires expertise in formulation science, engineering, digital design, and QC—all of which are not typically found in hospital or community pharmacy settings [91]. Infrastructure investment is also a barrier in low-resource healthcare environments.

6. Regulatory Landscape for 3D-Printed Medicines

The rapid emergence of 3D printing in pharmaceuticals has created an urgent need for updated regulatory frameworks. Traditional drug manufacturing regulations do not fully address the unique characteristics of additive manufacturing—such as digital design files, slicer settings, printer calibration, layer-by-layer variability, and decentralized point-of-care (POC) production [92]. Regulatory agencies worldwide are now working to adapt their guidelines to ensure safety, efficacy, and quality of 3D-printed medicines.

6.1 United States Food and Drug Administration (FDA)

The FDA is the global leader in regulating additive manufacturing for medical use. In 2015, the FDA approved Spritam®, the first 3D-printed oral dosage form, demonstrating the feasibility of additive manufacturing for human medicines [93].

Key FDA documents:

• Technical Considerations for Additive Manufactured Medical Devices (2017)
• Provides foundational requirements for design, manufacturing validation, and quality assurance [94].
• Guidance on Pharmaceutical Quality/CMC
• Addresses digital and process controls needed for novel manufacturing technologies [95].
• Emerging Technology Program (ETP)

Allows companies to engage early with FDA reviewers when using innovative manufacturing technologies, including 3D printing [96].

Regulatory focus areas include:

• Printer calibration, maintenance, and reproducibility
• Validation of CAD/CAM software and slicing parameters
• Layer adhesion quality and build orientation effects
• Material control (polymer grade, photoresins, residual monomers)
• In-process controls suitable for additive manufacturing
• Post-processing validation (curing, drying, sintering)

FDA is also evaluating point-of-care (POC) printing, where hospitals or pharmacies manufacture medicines onsite. Draft frameworks propose risk-based evaluation and identify when POC facilities require manufacturing licenses [97].

6.2 European Medicines Agency (EMA)

The EMA has acknowledged the growing interest in 3D-printed medicinal products. Although no specific EMA guidance exists exclusively for pharmaceuticals, several documents provide regulatory direction.

Relevant EMA positions:

• Manufacturers of 3D-printed drug products must comply with EU GMP Part I and II for quality systems, facilities, and manufacturing controls [98].
• Digital design files and printing parameters must be included in the Quality (Module 3) section of the marketing authorization dossier [99].
• Modifications to CAD files or printer settings require variation applications if they impact critical quality attributes (CQAs) [100].
• EMA has also published conceptual discussions on the implications of additive manufacturing for advanced therapy medicinal products (ATMPs) and personalized implants [101].

6.3 Central Drugs Standard Control Organization (CDSCO, India)

In India, the Central Drugs Standard Control Organization (CDSCO) has not yet released 3D-printing-specific pharmaceutical regulations, but existing frameworks apply:

Current regulatory applicability:

• New Drugs and Clinical Trial Rules (NDCT 2019) apply to clinical testing of 3D-printed dosage forms [102].
• Schedule M (Good Manufacturing Practices) applies to any facility manufacturing 3D-printed medicines [103].

Medical Device Rules apply to 3D-printed implants and biomedical devices.

Challenges for India include:

• Limited availability of pharmaceutical-grade printable materials
• Lack of trained regulatory reviewers for additive manufacturing
• Ambiguity regarding decentralized POC printing inside hospitals

CDSCO is expected to align its regulatory approach with FDA and EMA as adoption grows [104].

6.4 International Standards and Quality Frameworks

Several international organizations contribute standards relevant to pharmaceutical 3D printing:

ISO/ASTM 52900

Standard terminology and classification for additive manufacturing [105].

ICH Q8, Q9, Q10, Q12

Provide internationally harmonized frameworks for:

• Quality-by-design (QbD)
• Risk management
• Pharmaceutical quality systems
• Lifecycle change management
• These are increasingly applied to additive manufacturing workflows [106].
• USP & European Pharmacopoeia

Both have begun research initiatives to incorporate 3D-printed dosage form standards into future monographs [107].

6.5 Key Global Regulatory Challenges

Despite progress, several issues remain unresolved:

• Lack of specific GMP guidelines tailored to additive manufacturing
• Uncertainty around digital file security, version control, and cybersecurity
• No harmonized standard for printer validation and environmental control
• Need for new pharmacopeial tests for porosity, internal structure, and geometry
• Regulatory questions around POC printing responsibility (hospital vs. manufacturer)
• Limited toxicological data for photoresins and novel materials [108]

These regulatory uncertainties must be addressed to enable large-scale, routine use of 3D-printed medications.

7. Future Directions

Three-dimensional (3D) printing in pharmaceutics is transitioning from an experimental technology to a practical tool for personalized medicine. Future developments will be driven by advances in materials science, digital health, artificial intelligence, regulatory science, and manufacturing technologies [22,24,58,75]. Several promising directions are outlined below.

7.1 Integration of Artificial Intelligence and Machine Learning

Artificial intelligence (AI) and machine learning (ML) can optimize multiple aspects of pharmaceutical 3D printing, including:

• Predicting printability based on material properties
• Designing internal geometries for desired release profiles
• Optimizing process parameters (temperature, speed, infill, layer height)
• Personalizing dose strength based on patient-specific data

AI-driven models can be integrated with computer-aided design (CAD) and computer-aided manufacturing (CAM) to create fully automated “design–print–verify” workflows [22,60,71,74]. In the long term, AI may support real-time process control and self-correcting printing systems.

7.2 4D Printing and Stimuli-Responsive Systems

4D printing extends 3D printing by incorporating time as a functional dimension—allowing structures to change shape or behavior in response to external stimuli such as pH, temperature, moisture, or enzymes [22]. In pharmaceutics, this may enable:

• Gastroretentive systems that expand or unfold in the stomach
• Site-specific release in the intestine or colon based on pH
• Swellable or shrinkable implants for controlled mechanical interaction
• Pulsatile systems that respond to circadian rhythms or biomarker levels

Stimuli-responsive polymers and smart hydrogels will be essential for realizing these applications [58,80].

7.3 Development of Novel Printable Materials

There is a growing need for pharmaceutically acceptable printable materials with controlled melting points, rheology, and biocompatibility [25,79,80]. Future research will focus on:

• Biodegradable thermoplastic polymers for FDM with low processing temperatures
• Biocompatible photopolymers for SLA/DLP with minimal residual monomer toxicity [90]
• Hybrid bioinks for semi-solid extrusion and bioprinting [23,52,53]

Composite systems combining polymers, lipids, and inorganic components for tailored release [71] Regulatory acceptance of such materials will require robust toxicological and stability data [75,108].

7.4 Expansion of Point-of-Care and Decentralized Manufacturing

Point-of-care (POC) 3D printing in hospital and community pharmacy settings is one of the most disruptive future directions. In this model, prescriptions are translated into customized dosage forms directly at the treatment site [19,42,56,57].

Future developments may include:

• Integrated prescribing systems that automatically generate print files
• Compact, GMP-compliant printers dedicated to oral dosage forms
• Standardized hospital protocols for validation and QC
• Regulatory frameworks clearly defining responsibilities for POC manufacturers [92–97]

This decentralization has the potential to revolutionize access to personalized medicines, particularly in pediatrics, geriatrics, and rare diseases.

7.5 Bioprinting and Regenerative Medicine

Bioprinting—3D printing of living cells, biomaterials, and growth factors—opens the door to personalized regenerative therapies [23,52,53]. Potential pharmaceutical applications include:

• Patient-specific tissue scaffolds for bone, cartilage, or skin regeneration
• Bioprinted tumor models for individualized anticancer drug testing [54]
• Organ-on-chip platforms for preclinical drug screening
• Drug-eluting bioprinted grafts and implants

As bioinks and cell-compatible printing methods mature, bioprinting may become an integral component of personalized treatment protocols [52,53].

7.6 Digital Twins and In Silico Personalization

A “digital twin” is a virtual representation of a patient’s anatomical or physiological system, constructed from imaging, clinical, and genomic data. Combined with 3D printing, digital twins may be used to:

• Simulate drug release and pharmacokinetics from a printed dosage form before manufacturing
• Optimize implant shape and mechanical behavior based on patient-specific anatomy [52]
• Predict therapeutic outcomes under different dosing scenarios

Integrating pharmacometric models with CAD software could enable automated, simulation-driven design of personalized dosage forms [24,60,74].

7.7 Blockchain, Data Security, and File Traceability

Because 3D printing relies heavily on digital design files, maintaining data integrity and preventing unauthorized modifications are critical [74,92,96]. Blockchain technology and secure version control systems may be used to:

• Track all modifications to print files
• Ensure only validated designs are used for clinical manufacturing
• Provide an auditable trail for regulatory review
• Protect intellectual property and prevent counterfeit medicines

Such systems will support regulatory requirements for digital traceability [92–97,108].

7.8 Sustainability and Green Manufacturing

3D printing offers advantages in material efficiency and waste reduction compared with traditional subtractive processes [25,73]. Future directions include:

• Use of biodegradable, renewable polymers
• Energy-efficient printers and curing systems
• Design of dosage forms that minimize packaging needs
• Recycling and reusing powder in SLS and BJ-3DP processes [73,80]

Sustainable design principles will increasingly shape the development and assessment of pharmaceutical 3D printing technologies.

7.9 Toward Fully Integrated Personalized Medicine Ecosystems

Ultimately, pharmaceutical 3D printing is expected to become part of an integrated personalized medicine ecosystem, in which:

1. Patient-specific data (age, weight, genomics, comorbidities) are captured in electronic health records.

2. AI-powered algorithms determine the optimal dose, dosage form, and release profile [22,60,71,74].

3. CAD software generates a tailored dosage form design.

4. A validated 3D printer fabricates the medicine on demand.

5. Treatment outcomes are monitored and fed back into the system, further refining future prescriptions.

This closed-loop, data-driven cycle could dramatically improve therapeutic outcomes and move healthcare closer to the ideal of truly individualized therapy [24,42,58,75].

CONCLUSION

Three-dimensional (3D) printing represents one of the most transformative innovations in pharmaceutical science and personalized medicine. Its digitally controlled, layer-by-layer fabrication enables unprecedented customization of drug products, including precise dose adjustment, controlled-release behavior, multi-drug polypills, and complex geometries that are unachievable with traditional manufacturing methods [24,42,58,75]. These capabilities address critical unmet needs in special populations such as pediatrics [43–45], geriatrics [46,47], and oncology patients requiring individualized dosing strategies [54,55]. A wide range of 3D printing technologies—including FDM, SSE, SLS, SLA/DLP, inkjet printing, and hybrid processes—have been successfully adapted for pharmaceutics, enabling both clinical and research applications [7–12,28–40]. Despite this progress, several limitations must be overcome to achieve widespread clinical adoption. These include regulatory uncertainties [92–100], material constraints [79,80], stability and thermal degradation issues [81–84], scalability challenges [85,86], and quality control variability inherent to additive manufacturing processes [87–89]. Looking forward, the integration of artificial intelligence, machine learning, and digital twins promises to revolutionize design, optimization, and quality control of printed dosage forms [22,60,71,74]. The emergence of 4D printing, smart biomaterials, and bioprinting will enable dynamic and biologically relevant structures for advanced drug delivery and tissue engineering [22,23,52,53]. Additionally, decentralised point-of-care (POC) manufacturing models will allow hospitals and pharmacies to produce patient-specific medicines on demand, significantly improving accessibility and reducing dependency on large-scale centralized production [19,42,56,57]. To fully realize this vision, regulatory frameworks must evolve to address digital workflow validation, printer qualification, material toxicity, design file traceability, and consistent product quality [92–108]. Strong collaboration among academia, industry, clinicians, and regulatory bodies will be essential to drive innovation while ensuring patient safety. In conclusion, pharmaceutical 3D printing has already begun reshaping the future of personalized medicine. With continued advancements in materials, manufacturing technologies, and regulatory science, 3D printing is poised to become an integral component of precision therapeutics—bringing healthcare closer to delivering truly individualized treatments for patients worldwide.

REFERENCES

1. Raut A, Chavan R, Bhise S. Opportunities and challenges in personalized medicine. Drug Dev Res. 2019;80(3):249-256.
2. van Riet-Nales DA, de Neef BJ, Schobben AF, et al. The accuracy, precision and sustainability of splitting scored tablets. Arch Dis Child. 2016;101(2):193-199.
3. Kairuz TE, Gargiulo D, Bunt C, Garg S. Quality, safety and efficacy in the ‘off-label’ use of medicines. Curr Drug Saf. 2007;2(1):89-95.
4. Ventola CL. Medical applications for 3D printing: review. P T. 2014;39(10):704-711.
5. Jamróz W, Szafraniec J, Kurek M, Jachowicz R. 3D printing in pharmaceutical and medical applications. Pharm Res. 2018;35(8):176.
6. U.S. FDA. FDA approves the first 3D printed drug. 2015.
7. Goyanes A, Buanz ABM, Hatton GB, Gaisford S, Basit AW. 3D printing of modified-release oral dosage forms. Int J Pharm. 2015;487(1–2):144-151.
8. Skowyra J, Pietrzak K, Alhnan MA. Fabrication of extended-release patient-tailored 3D printed tablets. Int J Pharm. 2015;494(2):574-583.
9. Melocchi A, Uboldi M, Cerea M, et al. FDM 3D printing of medicines: quality evaluation of tablets. Int J Pharm. 2020;583:119397.
10. Li Q, Guan X, Cui M, Zhu Z, Chen K, Wen H. Preparation and investigation of novel gastro-floating tablets via 3D printing. Drug Dev Ind Pharm. 2018;44(12):1917-1925.
11. Scoutaris N, Ross SA, Douroumis D. Current trends on 3D printed pharmaceuticals. J Drug Deliv Sci Technol. 2011;21(6):367-377.
12. Awad A, Trenfield SJ, Goyanes A, et al. 3D printing: progress toward personalized medicine. Med Devices. 2021;14:95-105.
13. Aho J, Boetker JP, Baldursdottir S, et al. Pharmaceutical 3D printing in a hospital setting for pediatric medicine. Int J Pharm. 2019;566:394-403.
14. Khaled SA, Burley JC, Alexander MR, Roberts CJ. 3D printing of tablets for elderly patients. Eur J Pharm Sci. 2015;70:57-66.
15. Khaled SA, Alexander MR, Wildman RD, et al. 3D printing of five-drug polypills. Int J Pharm. 2015;494(2):643-650.
16. Zhang J, Xu P, Vo AQ, et al. Shape-dependent drug release from 3D printed tablets. J Pharm Sci. 2017;106(11):3171-3179.
17. Chung HJ, Park TG. Advanced drug delivery via implantable devices. Adv Drug Deliv Rev. 2012;64(14):1547-1562.
18. Economidou SN, Holländer J, Zhang Y, et al. 3D printed pharmaceutical-oncology formulations. Int J Pharm. 2019;558:19-30.
19. Awad A, Fina F, Goyanes A, et al. 3D printing at point of care. Int J Pharm. 2020;580:119340.
20. Norman J, Madurawe RD, Moore CM, Khan MA, Khairuzzaman A. A review of the assessment of 3D printed drug products. Nat Rev Drug Discov. 2017;16(6):421-437.
21. Ahn JB, Son JI, Lee J. Pharmaceutical 3D printing technology: regulatory considerations. J Pharm Investig. 2020;50:337-348.
22. He Y, Yang F, Zhao H, et al. Research on 4D printing: materials and applications. Biofabrication. 2020;12(4):042002.
23. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773-785.
24. Trenfield SJ, Awad A, Goyanes A, et al. 3D printing in pharmaceutical drug delivery. J Control Release. 2018;285:157–167.
25. Alhnan MA, Okwuosa TC, Sadia M, et al. Emergence of 3D printing in pharmaceutics. Adv Drug Deliv Rev. 2018;132:155–168.
26. Vithani K, Goyanes A, Jannin V, et al. Opportunities of additive manufacturing in drug product design. Int J Pharm. 2021;597:120303.
27. Awad A, Fina F, Gaisford S, Basit AW. 3D printing for pharmaceuticals. Addit Manuf. 2021;36:101690.
28. Katstra WE, Palazzolo RD, Rowe CW, et al. Oral dosage forms fabricated by 3D printing. J Control Release. 2000;66(1):1–9.
29. Yu DG, Yang XL, Huang WD, et al. Fast disintegrating 3D printed tablets. Int J Pharm. 2017;524(1–2):135–142.
30. Melocchi A, Parietti F, Loreti G, et al. FDM materials for pharmaceutical applications. J Drug Deliv Sci Technol. 2018;52:820–831.
31. Goyanes A, Det-Amornrat U, Wang J, et al. Chronotherapeutic FDM tablets. Addit Manuf. 2016;11:76–82.
32. Genina N, Holländer J, Jukarainen H, et al. Semi-solid extrusion in pharmaceuticals. Int J Pharm. 2016;500(1–2):79–87.
33. Alhijjaj M, Belton P, Qi S. Stability of semi-solid printed formulations. Eur J Pharm Sci. 2016;93:420–430.
34. Fina F, Goyanes A, Madla CM, et al. SLS for pharmaceutical production. Int J Pharm. 2018;547(1–2):44–52.
35. Trenfield SJ, Madla CM, Basit AW, Gaisford S. SLS in drug delivery. Addit Manuf. 2019;30:100884.
36. Martinez PR, Goyanes A, Basit AW, Gaisford S. SLA for pharmaceutical applications. Int J Pharm. 2017;532(2):602–610.
37. Economidou SN, Uddin MJ, Marques M, et al. SLA microneedles. Pharmaceutics. 2020;12(9):866.
38. Buanz ABM, Saunders MH, Basit AW, Gaisford S. Inkjet printing of APIs. Int J Pharm. 2011;414(1–2):7–12.
39. Scoutaris N, Ross SA, Douroumis D. Inkjet-based drug delivery. J Pharm Sci. 2011;100(8):3217–3226.
40. Khaled SA, Burley JC, Alexander MR, et al. Multi-workflow hybrid printing. Int J Pharm. 2015;494(2):577–584.
41. Mathur V, Dhanawat M. Personalized 3D printed medicines. Biomed Pharmacother. 2021;137:111351.
42. Trenfield SJ, Basit AW, Gaisford S. Advantages of 3D printing for personalized therapies. Expert Opin Drug Deliv. 2019;16(5):467–478.
43. Aho J, Boetker JP, Baldursdottir S, et al. Pediatric pharmaceutical 3D printing. Int J Pharm. 2019;566:394–403.
44. Goyanes A, Martínez PR, Buanz AB, et al. Pediatric-friendly 3D printlets. Int J Pharm. 2016;500(1–2):234–243.
45. Öblom H, Söderling E, Žagar J, et al. Hospital-based 3D printing of pediatric drugs. J Pharm Sci. 2020;109(7):1961–1969.
46. Parikh T, Ramprasad D, Jones M. Personalized medicines for geriatrics. Ther Adv Drug Saf. 2020;11:1–13.
47. Melocchi A, Cerea M, Uboldi M, et al. FDM for elderly patients. Eur J Pharm Sci. 2020;155:105558.
48. Khaled SA, Burley JC, Alexander MR, et al. 3D printed polypills. Eur J Pharm Biopharm. 2018;130:96–107.
49. Khaled SA, Alexander MR, Wildman RD, Roberts CJ. Multi-drug polypills by 3D printing. Int J Pharm. 2015;494(2):643–650.
50. Goyanes A, Buanz AB, Hatton GB, Gaisford S, Basit AW. Drug release modulation via 3D geometry. Addit Manuf. 2016;5:14–22.
51. Zhang J, Vo AQ, Wen H, et al. Shape-dependent release in 3D printed tablets. J Pharm Sci. 2017;106(11):3171–3179.
52. Hölzl K, Lin S, Tytgat L, et al. Biofabrication for implants. Adv Mater. 2016;28(34):5391–5420.
53. Murphy SV, Atala A. 3D bioprinting of tissues. Nat Biotechnol. 2014;32(8):773–785.
54. Economidou SN, Holländer J, Zhang Y, et al. Oncology-specific printlets. Int J Pharm. 2019;558:19–30.
55. Park SA, Lee SH, Kim WD. Drug-loaded PLA implants. Biomed Eng Lett. 2019;9:153–161.
56. Awad A, Fina F, Goyanes A, et al. POC 3D printing. Int J Pharm. 2020;580:119340
57. Genina N, Holländer J, Jukarainen H, et al. Extrusion printing at POC. Int J Pharm. 2016;500(1–2):79–87.
58. Vakili H, Wickström H, Desai D, Preis M, Sandler N. 3D printed dosage forms: opportunities and challenges. J Pharm Pharmacol. 2017;69(5):575–585.
59. Alhnan MA, Okwuosa TC, Sadia M, et al. Emergence of 3D printing in pharmaceutics. Adv Drug Deliv Rev. 2018;132:155–168.
60. Trenfield SJ, Awad A, Madla CM, et al. Shaping the future: 3D printed patient-specific oral dosage forms. J Control Release. 2019;295:21–30.
61. Scoutaris N, Ross SA, Douroumis D. Current trends on 3D printed pharmaceuticals. J Drug Deliv Sci Technol. 2011;21(6):367–377.
62. Goyanes A, Buanz ABM, Hatton GB, Gaisford S, Basit AW. 3D printing of modified-release prednisolone tablets. Int J Pharm. 2015;494(2):568–577.
63. Domsta V, Serra C, Witschnigg A, et al. Tailored drug release from 3D printed tablets via infill modulation. Eur J Pharm Biopharm. 2020;152:91–101.
64. Zhang J, Xu P, Vo AQ, et al. Development of 3D printed tablets with controlled zero-order drug release. J Pharm Sci. 2018;107(8):2221–2233.
65. Ahlholm H, Alopaeus JF, Reßing K, et al. Impact of geometry on drug release from 3D printed dosage forms. Eur J Pharm Sci. 2021;159:105734.
66. Gioumouxouzis CI, Katsamenis OL, Bouropoulos N, Fatouros DG. 3D printed COVID-19 polypills: design and manufacturing. Int J Pharm. 2022;613:121383.
67. Tiwari R, Singh N, Singh A, et al. 3D printed polypills for elderly patients: a patient-centric approach. Ther Innov Regul Sci. 2021;55(4):799–810.
68. Skowyra J, Pietrzak K, Alhnan MA. Personalized patient-tailored 3D printed tablets at the point of care. Int J Pharm. 2015;494(2):574–583.
69. Goyanes A, Martínez PR, Buanz ABM, et al. Acceptability of 3D printed chewable medicines in pediatrics. Int J Pharm. 2016;500(1–2):234–243.
70. Mistry P, Batchelor H. Pediatric oral medicines: acceptability of novel 3D printed formulations. Pharmaceutics. 2017;9(4):50.
71. Awad A, Trenfield SJ, Goyanes A, et al. Advances in 3D printing of oral dosage forms. Adv Drug Deliv Rev. 2018;132:35–48.
72. Gaisford S, Basit AW. The future of 3D printing in drug development and clinical practice. Pharmaceutics. 2018;10(2):E63.
73. Fina F, Goyanes A, Madla CM, et al. Powder recycling and mechanical properties in SLS-printed pharmaceuticals. Int J Pharm. 2018;547(1–2):44–52.
74. Trenfield SJ, Madla CM, Basit AW, Gaisford S. Digital health and 3D printing: a synergy for personalized therapy. Adv Drug Deliv Rev. 2022;176:113853
75. Norman J, Madurawe RD, Moore CMV, Khan MA, Khairuzzaman A. A review of 3D printed drug products. Nat Rev Drug Discov. 2017;16(6):421–437.
76. Ahn JB, Son JI, Lee J. Regulatory perspectives on pharmaceutical 3D printing. J Pharm Investig. 2020;50:337–348.
77. U.S. FDA. Technical considerations for additive manufactured medical devices. 2017.
78. European Medicines Agency (EMA). Reflection paper on 3D printing of medicinal products. 2020.
79. Melocchi A, Parietti F, Loreti G, et al. Pharmaceutical-grade polymers for FDM. J Drug Deliv Sci Technol. 2018;52:820–831.
80. Vithani K, Goyanes A, Jannin V, et al. Additive manufacturing in drug product design. Int J Pharm. 2021;597:120303.
81. Sadia M, Arafat B, Ahmed W, et al. Thermal effects on 3D printed drugs. Int J Pharm. 2018;538(1-2):167–176.
82. Zhang J, Yang W, Vo AQ, et al. Effects of printing temperature on drug crystallinity. Int J Pharm. 2017;528(1–2):138–148.
83. Genina N, Holländer J, Jukarainen H, et al. Stability of SSE printed drugs. Int J Pharm. 2016;500(1–2):79–87.
84. Goyanes A, Det-Amornrat U, Wang J, et al. Stability study of 3D printed tablets. Addit Manuf. 2016;11:76–82.
85. Alhijjaj M, Belton P, Qi S. Scale-up challenges in 3D printing. Eur J Pharm Sci. 2016;93:420–430.
86. Trenfield SJ, Awad A, Goyanes A, et al. Hybrid manufacturing for personalized tablets. Adv Drug Deliv Rev. 2018;132:35–48.
87. Fadda M, Balestra M, Melocchi A, et al. Variability in 3D printed dosage forms. Int J Pharm. 2021;605:120770.
88. Tagami T, Nagata N, Hayashi N, et al. PAT for additive manufacturing of pharmaceuticals. Int J Pharm. 2017;517(1–2):138–147.
89. Li Q, Guan X, Cui M, et al. Post-processing impact in 3D printing. Drug Dev Ind Pharm. 2018;44(12):1917–1925.
90. Marques M, Economidou SN, Lilienberg E, et al. Toxicological considerations of SLA printed drug products. Pharmaceutics. 2020;12(9):866.
91. Gaisford S, Basit AW. Implementation barriers for 3D printing in healthcare. Pharmaceutics. 2018;10(2):63.
92. Ahlholm H, Alopaeus JF, Reßing K, et al. Regulatory considerations for 3D printed pharmaceuticals. Eur J Pharm Sci. 2021;159:105734.
93. U.S. FDA. First FDA-approved 3D printed drug: Spritam (2015).
94. 94. U.S. FDA. Technical Considerations for Additive Manufactured Medical Devices. 2017.
95. U.S. FDA. Guidance for Industry: Q8(R2), Q9 & Q10 Pharmaceutical Quality System.
96. FDA Emerging Technology Program (ETP). Official FDA Website.
97. FDA Discussion Paper: 3D Printing at Point-of-Care. 2021.
98. European Medicines Agency. EU Guidelines for Good Manufacturing Practice.
99. EMA Quality Module 3 Guidance for Medicinal Products.
100. EMA Guideline on Variations to Marketing Authorizations.
101. EMA Reflection Paper on Advanced Therapy Medicinal Products.
102. CDSCO. New Drugs and Clinical Trials Rules (NDCT). 2019.
103. CDSCO. Schedule M: Good Manufacturing Practices for Pharmaceuticals.
104. Raut S, Rathod S, Deshpande S. Regulatory overview of 3D printed medicines in India. Indian J Pharm Educ Res. 2021;55(4):1267–1274.
105. ISO/ASTM 52900: Additive Manufacturing — General Principles.
106. ICH. Pharmaceutical Quality Guidelines Q8, Q9, Q10, Q12.
107. United States Pharmacopeia. USP Emerging Technologies.
108. Marques M, Economidou SN, Uddin MJ, et al. Toxicological risks of 3D printed pharmaceuticals. Pharmaceutics. 2020;12(9):866.