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Pharmaceutics
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3D Printing of Drug Delivery Systems
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3D Printing of Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 10404

Special Issue Editor

Dr. Djordje Medarevic

E-Mail Website
Guest Editor
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia
Interests: poorly soluble drugs; solid dispersions; amorphous formulation; nanocrystals; experimental design; 3D printing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Disease treatment is still largely based on a so-called one-size-fits-all approach, in which similar drug doses are prescribed to a large number of patients without taking into account the interindividual differences between them. In addition to tailoring therapy to the anatomical and physiological characteristics of individual patients, the acceptability of therapy to individual patients in terms of the dosing frequency, the number of drugs in therapy, and the appearance, size, colour, taste and textural properties of the dosage form is becoming increasingly important. The application of 3D printing technology offers practitioners the ability to produce small batches of drug delivery systems customized to individual patient characteristics and preferences, and provide tailored drug release. Since the FDA approved the first 3D-printed drug Spritam®, interest in the pharmaceutical application of 3D printing has been expanding in both academia and industry, leading to a number of publications and the appearance of the first 3D printers specifically designed for pharmaceutical purposes. However, further intensive research is required, and should focus in particular on the material properties and parameters of the printing process; these should be controlled in order to obtain a consistent product. A less stringent regulatory approach compared to conventional pharmaceutical production is certainly needed for the implementation of 3D printing at the point-of-care, where the benefits of this technology can be best exploited.

This Special Issue welcomes both original and review articles that address recent advances and future directions in the 3D printing of drug delivery systems.

Dr. Djordje Medarevic
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • additive manufacturing
  • 3D printing
  • personalized drug delivery systems
  • tailored drug release

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Published Papers (6 papers)

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Research

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13 pages, 2729 KiB  
Article
Development of Novel Oral Delivery Systems Using Additive Manufacturing Technologies to Overcome Biopharmaceutical Challenges for Future Targeted Drug Delivery
by Micol Cirilli, Julius Krause, Andrea Gazzaniga, Werner Weitschies, Matteo Cerea and Christoph Rosenbaum
Pharmaceutics 2025, 17(1), 29; https://doi.org/10.3390/pharmaceutics17010029 - 27 Dec 2024
Cited by 1 | Viewed by 3297
Abstract
Background/Objectives: The development of targeted drug delivery systems for active pharmaceutical ingredients with narrow absorption windows is crucial for improving their bioavailability. This study proposes a novel 3D-printed expandable drug delivery system designed to precisely administer drugs to the upper small intestine, where [...] Read more.
Background/Objectives: The development of targeted drug delivery systems for active pharmaceutical ingredients with narrow absorption windows is crucial for improving their bioavailability. This study proposes a novel 3D-printed expandable drug delivery system designed to precisely administer drugs to the upper small intestine, where absorption is most efficient. The aim was to design, prototype, and evaluate the system’s functionality for organ retention and targeted drug release. Methods: The system was created using 3D printing technologies, specifically FDM and SLA, with materials such as PLA and HPMC. The device was composed of matrices and springs, with different spring geometries (diameter, coil number, and cross-sectional shape) being tested for strength and flexibility. A gastro-resistant string was used to maintain the device in a compact configuration until it reached the neutral pH environment of the small intestine, where the string dissolved. The mechanical performance of the springs was evaluated using a texture analyzer, and the ability of the system to expand upon pH change was tested in simulated gastrointestinal conditions. Results: The results demonstrated that the system remained in the space-saving configuration for two hours under acidic conditions. Upon a pH change to 6.8, the system expanded as expected, with opening times of 5.5 ± 1.2 min for smaller springs and 2.5 ± 0.3 min for larger springs. The device was able to regain its expanded state, suggesting its potential for controlled drug release in the small intestine. Conclusions: This prototype represents a promising approach for targeted drug delivery to the upper small intestine, offering a potential alternative for drugs with narrow absorption windows. While the results are promising, further in vivo studies are necessary to assess the system’s clinical potential and mechanical stability in real gastrointestinal conditions. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
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17 pages, 1496 KiB  
Article
Selective Laser Sintering 3D Printing of Carvedilol Tablets: Enhancing Dissolution Through Amorphization
by Nikola Pešić, Branka Ivković, Tanja Barudžija, Branka Grujić, Svetlana Ibrić and Djordje Medarević
Pharmaceutics 2025, 17(1), 6; https://doi.org/10.3390/pharmaceutics17010006 - 24 Dec 2024
Viewed by 997
Abstract
Background/Objectives: Selective laser sintering (SLS) is one of the most promising 3D printing techniques for pharmaceutical applications as it offers numerous advantages, such as suitability to work with already approved pharmaceutical excipients, the elimination of solvents, and the ability to produce fast-dissolving, porous [...] Read more.
Background/Objectives: Selective laser sintering (SLS) is one of the most promising 3D printing techniques for pharmaceutical applications as it offers numerous advantages, such as suitability to work with already approved pharmaceutical excipients, the elimination of solvents, and the ability to produce fast-dissolving, porous dosage forms with high drug loading. When the powder mixture is exposed to elevated temperatures during SLS printing, the active ingredients can be converted from the crystalline to the amorphous state, which can be used as a strategy to improve the dissolution rate and bioavailability of poorly soluble drugs. This study investigates the potential application of SLS 3D printing for the fabrication of tablets containing the poorly soluble drug carvedilol with the aim of improving the dissolution rate of the drug by forming an amorphous form through the printing process. Methods: Using SLS 3D printing, eight tablet formulations were produced using two different powder mixtures and four combinations of experimental conditions, followed by physicochemical characterization and dissolution testing. Results: Physicochemical characterization revealed that at least partial amorphization of carvedilol occurred during the printing process. Although variations in process parameters were minimal, higher temperatures in combination with lower laser speeds appeared to facilitate a greater degree of amorphization. Ultimately, the partial conversion to the amorphous form significantly improved the dissolution of carvedilol compared to its pure crystalline form. Conclusions: Obtained results suggest that the SLS 3D printing technique can be effectively used to convert poorly water-soluble drugs to their amorphous state, thereby improving solubility and bioavailability. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
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16 pages, 2988 KiB  
Article
Customizable Self-Microemulsifying Rectal Suppositories by Semisolid Extrusion 3D Printing
by Hye Jin Park and Dong Wuk Kim
Pharmaceutics 2024, 16(11), 1359; https://doi.org/10.3390/pharmaceutics16111359 - 24 Oct 2024
Viewed by 1502
Abstract
Objectives: This study aims to create an innovative self-microemulsifying drug delivery system (SMEDDS) suppository for ibuprofen (IBU) using semisolid extrusion (SSE) three-dimensional (3D) printing technology. Methods: Based on solubility studies and the ability to form a transparent microemulsion upon dilution, a [...] Read more.
Objectives: This study aims to create an innovative self-microemulsifying drug delivery system (SMEDDS) suppository for ibuprofen (IBU) using semisolid extrusion (SSE) three-dimensional (3D) printing technology. Methods: Based on solubility studies and the ability to form a transparent microemulsion upon dilution, a selected oil, surfactant, and co-surfactant were utilized to prepare SMEDDS-3DPS containing IBU. The optimal formulation consisted of 10% Triacetin, 80% Gelucire 48/16, and 10% Tetraethylene glycol. SSE 3D printing was employed to create three different-sized suppositories with varying drug contents. These suppositories were assessed for their physicochemical properties, content uniformity, and dissolution profiles. Results: The prepared mixture exhibited suitable physical properties for printing, with nano-sized emulsion droplets providing a large surface area for improved drug absorption in the rectum. Characterization techniques such as differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy indicated that IBU was present in the formulation in an amorphous state. Additionally, in vitro dissolution tests demonstrated that SMEDDS-3DPS had a significantly higher initial dissolution rate compared with IBU powder. Conclusions: This research suggests that SMEDDS-3DPS, as a rectal IBU dosage form, can enhance the rectal bioavailability of IBU. It demonstrates the versatility of 3D printing as a novel manufacturing method for lipid-based suppositories and highlights the simplicity and adaptability of SSE 3D printing technology in producing customized suppositories tailored to individual patient needs, surpassing traditional methods. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
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15 pages, 4188 KiB  
Article
Three-Dimensional Printing of PVA Capsular Devices for Applications in Compounding Pharmacy: Effect of Design Parameters on Pharmaceutical Performance
by Juan Francisco Peña, Ivana Cotabarren and Loreana Gallo
Pharmaceutics 2024, 16(8), 1069; https://doi.org/10.3390/pharmaceutics16081069 - 15 Aug 2024
Cited by 1 | Viewed by 1203
Abstract
The creation of products with personalized or innovative features in the pharmaceutical sector by using innovative technologies such as three-dimensional (3D) printing is particularly noteworthy, especially in the realm of compounding pharmacies. In this work, 3D printed capsule devices (CDs) with different wall [...] Read more.
The creation of products with personalized or innovative features in the pharmaceutical sector by using innovative technologies such as three-dimensional (3D) printing is particularly noteworthy, especially in the realm of compounding pharmacies. In this work, 3D printed capsule devices (CDs) with different wall thicknesses (0.2, 0.3, 0.4, 0.6, and 0.9 mm) and sizes were designed and successfully fabricated varying printing parameters such as extrusion temperature, printing speed, material flow percent, and nozzle diameter. The physicochemical, pharmaceutical, and biopharmaceutical performance of these CDs was evaluated with the aim of achieving an immediate drug release profile comparable to hard gelatin capsules (HGC) for use in magistral compounding. It was observed that the disintegration time of the CDs increased with wall thickness, which correlated with a slower drug release rate. CDs with configurations presenting 0.4 mm wall thickness and sizes comparable to HGC n° 0, 1, and 2 demonstrated satisfactory weight uniformity, short disintegration times, and immediate drug release, indicating their potential as effective devices in future compounding pharmacy applications. In addition, a modified Weibull-type model was proposed that incorporates wall thickness as a new variable in predicting dissolution profiles. This model improves the process of selecting a specific wall thickness to achieve the desired dissolution rate within a specified time frame. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
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13 pages, 2422 KiB  
Article
3D Screen Printing Offers Unprecedented Anticounterfeiting Strategies for Oral Solid Dosage Forms Feasible for Large Scale Production
by Nicolle Schwarz, Marcel Enke, Franka V. Gruschwitz, Daniela Winkler, Susanne Franzmann, Lisa Jescheck, Felix Hanf and Achim Schneeberger
Pharmaceutics 2024, 16(3), 368; https://doi.org/10.3390/pharmaceutics16030368 - 5 Mar 2024
Viewed by 1989
Abstract
A threat to human health in developed and, in particular, in developing countries, counterfeit medicines represent the largest identified fraud market worldwide. 3D screen printing (3DSP), an additive manufacturing technology that enables large-scale production, offers unique opportunities to combat counterfeit drugs. One such [...] Read more.
A threat to human health in developed and, in particular, in developing countries, counterfeit medicines represent the largest identified fraud market worldwide. 3D screen printing (3DSP), an additive manufacturing technology that enables large-scale production, offers unique opportunities to combat counterfeit drugs. One such possibility is the generation of oral dosage forms with a distinct colored inner structure that becomes visible upon breakage and cannot be copied with conventional manufacturing methods. To illustrate this, we designed tablets containing a blue cross. Owing to paste properties and the limited dimensions of the cross, the production process was chosen to be continuous, involving two screen and paste changes. The two pastes (tablet body, cross) were identical except for the blue color of the latter. This ensured the build-up and mechanical stability of the resulting tablets in a mass production environment. The ensuing tablets were found to be uniform in weight and size and to comply with regulatory requirements for hardness, friability, and disintegration time (immediate release). Moreover, all tablets exhibited the covert anticounterfeit feature. The study delivers a proof-of-concept for incorporating complex structures into tablets using 3DSP and showcases the power of the technology offering new avenues for combating counterfeit drugs. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
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Review

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26 pages, 4052 KiB  
Review
Use of Computational Intelligence in Customizing Drug Release from 3D-Printed Products: A Comprehensive Review
by Fantahun Molla Kassa, Souha H. Youssef, Yunmei Song and Sanjay Garg
Pharmaceutics 2025, 17(5), 551; https://doi.org/10.3390/pharmaceutics17050551 - 23 Apr 2025
Viewed by 462
Abstract
Computational intelligence (CI) mimics human intelligence by expanding the capabilities of machines in data analysis, pattern recognition, and making informed decisions. CI has shown promising contributions to advancements in drug discovery, formulation, and manufacturing. Its ability to analyze vast amounts of patient data [...] Read more.
Computational intelligence (CI) mimics human intelligence by expanding the capabilities of machines in data analysis, pattern recognition, and making informed decisions. CI has shown promising contributions to advancements in drug discovery, formulation, and manufacturing. Its ability to analyze vast amounts of patient data and optimize drug formulations by predicting pharmacokinetic and pharmacodynamic responses makes it a very useful platform for personalized medicine. The integration of CI with 3D printing further strengthens this potential, as 3D printing enables the fabrication of personalized medicines with precise doses, controlled-release profiles, and complex formulations. Furthermore, the automated and digital capabilities of 3D printing make it suitable for integration with CI. CI has proven useful in predicting material printability, optimizing drug release rates, designing complex structures, ensuring quality control, and improving manufacturing processes in 3D printing. In the context of customizing drug release from 3D-printed products, CI techniques have been applied to predict drug release from input variables and to design geometries that achieve the desired release profile. This review explores the role of CI in customizing drug release from 3D-printed formulations. It provides overview of limitations of 3D printing; how CI can overcome these challenges, and its potential in customizing drug release; a comparison of CI with other methods of optimization; and real-world examples of CI integration in 3D printing. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
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