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Pharmaceutical Applications of 3D Printing

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 16117

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Dr. Philippe Espeau

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UTCBS, Department of Pharmacy, University Paris Cité, 75006 Paris, France
Interests: pharmaceutical compound; solid state; relative stability; phase diagrams; thermodynamics; thermal analyses, 3D printing by FDM
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Special Issue Information

Dear Colleagues,

The use of 3D printing in the biomedical field has been developing since the 1980s. In August 2015, 3D printing was expanded to the pharmaceutical field and the first 3D printed tablet (printlet), Spritam®, was approved by the FDA. Since then, numerous studies have focused on the manufacture of printlets using different printing methods.

In contrast to traditional manufacturing technologies, the interest of 3D printing is growing due to flexible and adjustable manufacturing processes that allow for the accurate adjustment of shape, size, flavor and dosage. Indeed, the dosages required for children and seniors may be very different from those observed in adults due to physiological and pharmacokinetic differences. In addition, 3D printing allows us to control the location of drug release, e.g., to target a specific segment of the gastrointestinal tract to treat gastrointestinal disorders.

The innovative aspect of 3D printing is to combine multiple drugs, dosages and drug-release profiles into a single formulation leading to an improvement in therapeutic adherence. Therefore, the number of daily tablets and also the potential administration errors are reduced. Moreover, the 3D printing allows us to control the drug release for enhancing its pharmacokinetics and efficacy (e.g., once-a-day dosing or delayed release to extend the effect). This possibility would constitute a step forward for elderly people who are often polymedicated.

Regarding the pediatric population, the conventional formulations may not be suitable or are not available (e.g. solid form, low palatability or unsuitable dosages). In this context, 3D printing is a manufacturing technique that could enable us to meet the specific needs of each patient.

Thanks to 3D printing, the use of certain excipients which are the subject of intolerance in certain patients can be avoided. In particular, the pediatric formulations contain many excipients which might cause toxicity in children.

This Special Issue focuses on numerous possible pharmaceutical applications of 3D Printing. An overview of the different 3D printing techniques applied to the pharmaceutical field will be of interest for the scientific community.

Research articles and reviews are welcome, and we look forward to receiving your contributions.

Dr. Philippe Espeau
Guest Editor

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Keywords

3D printing
printlet
pharmaceutical application
dosage form
polymedication
personalized medicine

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Published Papers (10 papers)

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Research

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24 pages, 7262 KiB

Open AccessArticle

Developing Heterogeneous Porous 3D-Printed SiO₂-Pd-K₂SiO₃ Monolithic Catalyst via Surface MOF Growth and Pyrolysis for the Synthesis of Antitumoral Isatins

by Alexandrina Druta, Rania Bouhmala, Teqwa Ragdi, Mariangel Luna, Manuel Bañobre-López, Christian F. Masaguer, Manuel Amorín, Silvia Barbosa, Pablo Taboada and Alberto Coelho

Pharmaceutics 2025, 17(4), 505; https://doi.org/10.3390/pharmaceutics17040505 - 11 Apr 2025

Viewed by 475

Abstract

Background/Objectives: The isatin nucleus is a privileged scaffold in drug discovery, particularly due to its proven relevance in anticancer research. Developing reusable heterogeneous 3D catalysts for drug synthesis represents a critical challenge in both industrial and academic contexts. This multi and interdisciplinary work aimed to design and synthesize a novel 3D-printed silica-based porous catalyst functionalized with palladium, evaluate its catalytic performance in isatin drug synthesis, and assess the antiproliferative activity of the resulting compounds against tumor cell lines such as HeLa, MCF-7, and MDA-MB231. Methods: The novel multifaceted approach to synthesizing this heterogeneous catalyst involved the surface growth of a metal–organic framework (ZIF-8) on 3D-printed silica support, followed by potassium silicate coating and pyrolysis. Results: After detailed physicochemical characterization, the catalyst was tested in challenging “double” palladium-catalyzed cross-coupling reactions (Suzuki, Stille, and Heck), demonstrating robustness, reusability, and high efficiency in producing bis-1,5-aryl, alkynyl, and alkenyl-isatin derivatives. Importantly, no leaching of palladium species was detected during the catalytic cycles, further underscoring the stability of the system. These isatin-based compounds exhibited remarkable cytotoxicity, with selective molecules achieving nanomolar potency against MCF-7 cells, surpassing reference drugs such as doxorubicin and sunitinib. Conclusions: This study not only introduces a novel strategy for fabricating porous heterogeneous catalysts from sintered surfaces but also highlights new biomolecules with promising applications in cancer research. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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26 pages, 4274 KiB

Open AccessArticle

Exploring Manipulated Prescribed Medicines for Novel Leads in 3D Printed Personalized Dosage Forms

by Wouter Pannekoek, Eveline E. M. van Kampen, Frank van Tienen, P. Hugo M. van der Kuy and Elisabeth J. Ruijgrok

Pharmaceutics 2025, 17(2), 271; https://doi.org/10.3390/pharmaceutics17020271 - 18 Feb 2025

Viewed by 724

Abstract

Background: On-demand personalized drug production is currently not addressed with large-scale drug manufacturing. In our study, we focused primarily on identifying possible active pharmaceutical ingredients (APIs) for 3D Printing (3DP) in the current healthcare setting. Methods: We conducted a retrospective cross-sectional study in the Netherlands using three different sources; community pharmacies (n = 5), elderly care homes (n = 3), and the Erasmus MC Sophia Children’s Hospital. The primary endpoint was the percentage of prescriptions of medication manipulated before administration, thereby being a candidate for 3DP. Around a million prescriptions were analyzed in our study. Results: This study shows that around 3.0% of the prescribed drugs dispensed by Dutch community pharmacies were manipulated before administration, while around 10.5% of the prescribed drugs in the Erasmus MC Sophia Children’s Hospital were manipulated prior to administration. Conclusions: With our study, we show that the most manipulated drugs come from the groups of constipation, psychopharmaceutical, cardiovascular, and anti-infectant drugs. Successful introduction of a compounded API drug by 3DP does not only rely on the API, but it also comes with an optimal balance between technical, economic as well as societal impact factors. Our study gives direction for potential future research on the introduction of 3DP of medicine in the healthcare setting. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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17 pages, 4093 KiB

Open AccessArticle

3D-Printed Contact Lenses to Release Polyvinyl Alcohol as a Therapeutic Agent for the Treatment of Dry Eyes

by Piyush Garg, Parvin Shokrollahi, Haile Fentahun Darge, Chau-Minh Phan and Lyndon Jones

Pharmaceutics 2025, 17(2), 219; https://doi.org/10.3390/pharmaceutics17020219 - 8 Feb 2025

Viewed by 1388

Abstract

Purpose: Dry eye disease is highly prevalent, and the most common treatment, lubricating eye drops, only remains effective for a very short period of time. This project aims to 3D print a proof-of-concept, custom-fit, polyvinyl alcohol (PVA)-eluting contact lens (CL) for the treatment of dry eye disease. PVA is a commonly used viscosity enhancer in eye drops, with the capability of reducing symptoms of dry eye by stabilizing the tear film and reducing tear evaporation. The protective effects of PVA could be attributed to its water-retaining ability, which provides moisturization and prevents the loss of water. Method: In this work, a low-cost stereolithography-based 3D printer was retrofitted with a humidity and temperature control kit to 3D print a PVA-loaded custom-fit CL. To evaluate the print quality of the 3D-printed CL, circularity was used to evaluate the shape fidelity in 3D printing. The PVA release from these lenses was assessed, along with its role in acting as a viscosity enhancer. The effect of PVA was further analyzed by a dry eye disease (desiccation stress) cell model. Results: The shape fidelity evaluation of the 3D-printed CL displayed excellent circularity. The diameter, sagittal depth, and base curve of the 3D-printed lenses were measured to be 14.27 ± 0.06 mm, 3.77 ± 0.16 mm, and 6.4 ± 0.24 mm, respectively. The PVA release curves showed that approximately 1300 µg of PVA was released over the study duration of 24 h. Conclusions: Overall, this work demonstrates that a 3D-printed PVA-eluting CL is a promising candidate for the treatment of dry eye. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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19 pages, 4933 KiB

Open AccessArticle

Evaluating Swellable Cross-Linked Biopolymer Impact on Ink Rheology and Mechanical Properties of Drug-Contained 3D-Printed Thin Film

by Farzana Khan Rony, Jonathan Appiah, Asmaa Alawbali, Distinee Clay, Shamsuddin Ilias and Mohammad A. Azad

Pharmaceutics 2025, 17(2), 183; https://doi.org/10.3390/pharmaceutics17020183 - 1 Feb 2025

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Abstract

Background/Objectives: Interest in 3D printing oral thin films (OTFs) has increased substantially. The challenge of 3D printing is film printability, which is strongly affected by the rheological properties of the ink and having suitable mechanical properties. This research assesses the suitability of sodium starch glycolate (SSG), a swellable cross-linked biopolymer, on ink rheology and the film’s mechanical properties. Methods: A water-based ink comprising sodium alginate (SA), the drug fenofibrate (FNB), SSG, glycerin, and polyvinylpyrrolidone (PVP) was formulated, and its rheology was assessed through flow, amplitude sweeps, and thixotropy tests. Films (10 mm × 15 mm × 0.35 mm) were 3D-printed using a 410 µm nozzle, 50% infill density, 60 kPa pressure, and 10 mm/s speed, with mechanical properties (Young’s modulus, tensile strength, and elongation at break) analyzed using a TA-XT Plus C texture analyzer. Results: The rheology showed SSG-based ink has suitable properties (shear-thinning behavior, high viscosity, higher modulus, and quick recovery) for 3D printing. SSG enhanced the rheology (viscosity and modulus) of ink but not the mechanical properties of film. XRD and DSC confirmed preserved FNB crystallinity without polymorphic changes. SEM images showed surface morphology and particle distribution across the film. The film demonstrated a drug loading of 44.28% (RSD 5.62%) and a dissolution rate of ~77% within 30 min. Conclusions: SSG improves ink rheology, makes it compatible with 3D printing, and enhances drug dissolution (formulation F-5). Plasticizer glycerin is essential with SSG to achieve the film’s required mechanical properties. The study confirms SSG’s suitability for 3D printing of OTFs. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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16 pages, 3069 KiB

Open AccessEditor’s ChoiceArticle

An Antibacterial-Loaded PLA 3D-Printed Model for Temporary Prosthesis in Arthroplasty Infections: Evaluation of the Impact of Layer Thickness on the Mechanical Strength of a Construct and Drug Release

by Carlos Tamarit-Martínez, Lucía Bernat-Just, Carlos Bueno-López, Adrián M. Alambiaga-Caravaca, Virginia Merino, Alicia López-Castellano and Vicent Rodilla

Pharmaceutics 2024, 16(9), 1151; https://doi.org/10.3390/pharmaceutics16091151 - 30 Aug 2024

Viewed by 972

Abstract

Infections are one of the main complications in arthroplasties. These infections are difficult to treat because the bacteria responsible for them settle in the prosthesis and form a biofilm that does not allow antimicrobials to reach the infected area. This study is part of a research project aimed at developing 3D-printed spacers (temporary prostheses) capable of incorporating antibacterials for the personalized treatment of arthroplasty infections. The main objective of this research was to analyze the impact of the layer thickness of 3D-printed constructs based on polylactic acid (PLA) for improved treatment of infections in arthroplasty. The focus is on the following parameters: resistance, morphology, drug release, and the effect of antibacterials incorporated in the printed temporary prostheses. The resistance studies revealed that the design and layer thickness of a printed spacer have an influence on its resistance properties. The thickness of the layer used in printing affects the amount of methylene blue (used as a model drug) that is released. Increasing layer thickness leads to a greater release of the drug from the spacer, probably as a result of higher porosity. To evaluate antibacterial release, cloxacillin and vancomycin were incorporated into the constructs. When incorporated into the 3D construct, both antibacterials were released, as evidenced by the growth inhibition of Staphylococcus aureus. In conclusion, preliminary results indicate that the layer thickness during the three-dimensional (3D) printing process of the spacer plays a significant role in drug release. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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15 pages, 5014 KiB

Open AccessEditor’s ChoiceArticle

A Stereolithography-Based Modified Spin-Casting Method for Faster Laboratory-Scale Production of Dexamethasone-Containing Dissolving Microneedle Arrays

by Martin Cseh, Gábor Katona, Szilvia Berkó, Mária Budai-Szűcs and Ildikó Csóka

Pharmaceutics 2024, 16(8), 1005; https://doi.org/10.3390/pharmaceutics16081005 - 29 Jul 2024

Viewed by 1408

Abstract

Microneedle arrays (MNAs) consist of a few dozens of submillimeter needles, which tend to penetrate through the stratum corneum layer of the skin and deliver hardly penetrating drugs to the systemic circulation. The application of this smart dosage form shows several advantages, such as simple use and negligible pain caused by needle punctures compared to conventional subcutaneous injections. Dissolving MNAs (DMNAs) represent a promising form of cutaneous drug delivery due to their high drug content, biocompatibility, and ease of use. Although different technologies are suitable to produce microneedle arrays (e.g., micromilling, chemical etching, laser ablation etc.), many of these are expensive or hardly accessible. Following the exponential growth of the 3D-printing industry in the last decade, high-resolution desktop printers became accessible for researchers to easily and cost-effectively design and produce microstructures, including MNAs. In this work, a low force stereolithography (LFS) 3D-printer was used to develop the dimensionally correct MNA masters for the spin-casting method. The present study aimed to develop and characterize drug-loaded DMNAs using a two-level, full factorial design for three factors focusing on the optimization of DMNA production and adequate drug content. For the preparation of DMNAs, carboxymethylcellulose and trehalose were used in certain amounts as matrices for dexamethasone sodium phosphate (DEX). Investigation of the produced DexDMNAs included mechanical analysis via texture analyzer and optical microscopy, determination of drug content and distribution with HPLC and Raman microscopy, dissolution studies via HPLC, and ex vivo qualitative permeation studies by Raman mapping. It can be concluded that a DEX-containing, mechanically stable, biodegradable DexDMNA system was successfully developed in two dosage strengths, of which both efficiently delivered the drug to the lower layers (dermis) of human skin. Moreover, the ex vivo skin penetration results support that the application of DMNAs for cutaneous drug delivery can be more effective than that of a conventional dermal gel. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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17 pages, 2526 KiB

Open AccessEditor’s ChoiceArticle

Geometry-Driven Fabrication of Mini-Tablets via 3D Printing: Correlating Release Kinetics with Polyhedral Shapes

by Young-Jin Kim, Yu-Rim Choi, Ji-Hyun Kang, Yun-Sang Park, Dong-Wook Kim and Chun-Woong Park

Pharmaceutics 2024, 16(6), 783; https://doi.org/10.3390/pharmaceutics16060783 - 8 Jun 2024

Cited by 5 | Viewed by 1876

Abstract

The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R² = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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18 pages, 4768 KiB

Open AccessArticle

Evaluation of Printability of PVA-Based Tablets from Powder and Assessment of Critical Rheological Parameters

by Jonas Lenhart, Florian Pöstges, Karl G. Wagner and Dominique J. Lunter

Pharmaceutics 2024, 16(4), 553; https://doi.org/10.3390/pharmaceutics16040553 - 19 Apr 2024

Cited by 4 | Viewed by 1843

Abstract

Fused deposition modeling (FDM) is a rather new technology in the production of personalized dosage forms. The melting and printing of polymer–active pharmaceutical ingredient (API)—mixtures can be used to produce oral dosage forms with different dosage as well as release behavior. This process is utilized to increase the bioavailability of pharmaceutically relevant active ingredients that are poorly soluble in physiological medium by transforming them into solid amorphous dispersions (ASD). The release from such ASDs is expected to be faster and higher compared to the raw materials and thus enhance bioavailability. Printing directly from powder while forming ASDs from loperamide in Polyvinylalcohol was realized. Different techniques such as a change in infill and the incorporation of sorbitol as a plastisizer to change release patterns as well as a non-destructive way for the determination of API distribution were shown. By measuring the melt viscosities of the mixtures printed, a rheological model for the printer used is proposed. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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Review

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27 pages, 3876 KiB

Open AccessReview

Revealing Three-Dimensional Printing Technology Advances for Oral Drug Delivery: Application to Central-Nervous-System-Related Diseases

by Samir I. Paipa-Jabre-Cantu, Marisela Rodriguez-Salvador and Pedro F. Castillo-Valdez

Pharmaceutics 2025, 17(4), 445; https://doi.org/10.3390/pharmaceutics17040445 - 31 Mar 2025

Viewed by 661

Abstract

Background/Objectives. Central nervous system (CNS)-related diseases such as Alzheimer’s and Parkinson’s, Attention Deficit Hyperactive Disorder (ADHD), stroke, epilepsy, and migraines are leading causes of morbidity and disability worldwide. New solutions for drug delivery are increasingly needed. In this context, three-dimensional (3D) printing technology has introduced innovative alternatives to produce more efficient medicines with diverse features, patterns, and consistencies, particularly oral medications. Even though research in this area is growing rapidly, no study has thoroughly analyzed 3D printing oral drug delivery progress for the CNS. To fill this gap this study pursues to determine a technological landscape in this field. Methods. For this aim, a Competitive Technology Intelligence (CTI) methodology was applied, examining 747 publications from 1 January 2019 to 20 May 2024 published in the Scopus database. Results. The main advances identified comprise six categories: 3D printing techniques, characteristics and applications, materials, design factors, user acceptance, and quality processes. FDM was identified as the main technique for pharmaceutical use. The main applications include pills, polypills, caplets, gel caps, multitablets, orodispersible films, and tablets, featuring external patterns and internal structures with one or more active substances. Insights show that the most utilized materials are thermoplastic polymers like PLA, PVA, PCL, ABS, and HIPS. A novel design factor involves release patterns using compartments of varying thicknesses and volumes in the core. Additionally, advances in specialized software have enabled the creation of highly complex designs. In the user acceptance category, oral drugs dosages are tailored to the specific needs and preferences of neurological patients. Finally, for the quality aspect, the precision in Active Pharmaceutical Ingredient (API) dosage and controlled-release mechanisms are critical, given the narrow margin between therapeutic doses and toxicity for CNS diseases. Conclusions. Revealing these advancements in 3D printing for oral drug delivery allows researchers, academics, and decision-makers to identify opportunities and allocate resources efficiently, promising enhanced oral medicaments for the health and well-being of individuals suffering from CNS disorders. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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21 pages, 2069 KiB

Open AccessReview

Pediatric Formulations Developed by Extrusion-Based 3D Printing: From Past Discoveries to Future Prospects

by Veronica Ianno, Sarah Vurpillot, Sylvain Prillieux and Philippe Espeau

Pharmaceutics 2024, 16(4), 441; https://doi.org/10.3390/pharmaceutics16040441 - 22 Mar 2024

Cited by 9 | Viewed by 2460

Abstract

Three-dimensional printing (3DP) technology in pharmaceutical areas is leading to a significant change in controlled drug delivery and pharmaceutical product development. Pharmaceutical industries and academics are becoming increasingly interested in this innovative technology due to its inherent inexpensiveness and rapid prototyping. The 3DP process could be established in the pharmaceutical industry to replace conventional large-scale manufacturing processes, particularly useful for personalizing pediatric drugs. For instance, shape, size, dosage, drug release and multi-drug combinations can be tailored according to the patient’s needs. Pediatric drug development has a significant global impact due to the growing needs for accessible age-appropriate pediatric medicines and for acceptable drug products to ensure adherence to the prescribed treatment. Three-dimensional printing offers several significant advantages for clinical pharmaceutical drug development, such as the ability to personalize medicines, speed up drug manufacturing timelines and provide on-demand drugs in hospitals and pharmacies. The aim of this article is to highlight the benefits of extrusion-based 3D printing technology. The future potential of 3DP in pharmaceuticals has been widely shown in the last few years. This article summarizes the discoveries about pediatric pharmaceutical formulations which have been developed with extrusion-based technologies. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of 3D Printing)

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