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3D Printing for Chemical, Pharmaceutical, and Biological Applications

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 21076

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Special Issue Editors

Prof. Dr. Markus Thommes

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Guest Editor

Department of Biochemical and Chemical Engineering, TU Dortmund University, Dortmund, Germany
Interests: pharmceutical porcess design; process and fromulation develpoment; hot melt extrusion; spray drying; granulation; milling

Dr. Julian Quodbach

E-Mail Website
Guest Editor

Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
Interests: pharmaceutical 3D printing (fused deposition modeling, semisolid extrusion, selective laser sintering, binder jetting); hot-melt extrusion; process analytical technologies; fluidized bed processes

Special Issue Information

Dear Colleagues,

3D printing technologies are rapidly changing manufacturing processes and process chains as we know them in a number of industries. In many industries, 3D printing is already an established technique for direct manufacturing of functional end-products. Numerous examples show that an increased productivity can be achieved without trade-offs regarding precision or durability, enabling approaches and ideas previously thought impossible or too expensive to realize.

In research, 3D printing not only enables the fast realization of new ideas but also generates new interdisciplinary needs for technologies and applied materials, which are in the focus of scientists.

Even the potential advantages of existing applications are almost inexhaustible. The ability to precisely target the deposition of different materials in low quantities allows novel designs in many research fields, such as drug dosage design and individualization, tissue engineering or scaffolding. 3D printing is used to realize complex micro- and macrofluidic applications, and chemical reactors and electrochemical cells can be improved with these technologies.

This Special Issue covers all chemical, pharmaceutical, and biologial applications of 3D printing.

Prof. Dr. Markus Thommes
Dr. Julian Quodbach
Guest Editors

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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

dosage form design and application
process and formulation development
micro- and macrofluidics
polymers and excipients
tissue engineering and scaffolds

Published Papers (6 papers)

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Research

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15 pages, 3493 KiB

Open AccessArticle

Influence of Drug Load on the Printability and Solid-State Properties of 3D-Printed Naproxen-Based Amorphous Solid Dispersion

by Eric Ofosu Kissi, Robin Nilsson, Liebert Parreiras Nogueira, Anette Larsson and Ingunn Tho

Molecules 2021, 26(15), 4492; https://doi.org/10.3390/molecules26154492 - 26 Jul 2021

Cited by 10 | Viewed by 2841

Abstract

Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon^® VA 64 at 10–30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC and XRPD analysis, it was found that the drug in the 3D-printed tablets (20 and 30% NAP) was amorphous and remained amorphous after 23 weeks of storage (room temperature (RT), 37% relative humidity (RH)). This shows that adjusting the drug ratio can modulate the brittleness and improve printability without compromising the physical stability of the amorphous solid dispersion. Full article

(This article belongs to the Special Issue 3D Printing for Chemical, Pharmaceutical, and Biological Applications)

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12 pages, 5696 KiB

Open AccessArticle

3D Printing of Drug Nanocrystals for Film Formulations

by Giorgia Germini and Leena Peltonen

Molecules 2021, 26(13), 3941; https://doi.org/10.3390/molecules26133941 - 28 Jun 2021

Cited by 28 | Viewed by 3770

Abstract

The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2–3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations. Full article

(This article belongs to the Special Issue 3D Printing for Chemical, Pharmaceutical, and Biological Applications)

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22 pages, 5689 KiB

Open AccessFeature PaperArticle

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

by Jolanta Pyteraf, Witold Jamróz, Mateusz Kurek, Joanna Szafraniec-Szczęsny, Daniel Kramarczyk, Karolina Jurkiewicz, Justyna Knapik-Kowalczuk, Jacek Tarasiuk, Sebastian Wroński, Marian Paluch and Renata Jachowicz

Molecules 2021, 26(11), 3106; https://doi.org/10.3390/molecules26113106 - 22 May 2021

Cited by 9 | Viewed by 2699

Abstract

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics. Full article

(This article belongs to the Special Issue 3D Printing for Chemical, Pharmaceutical, and Biological Applications)

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10 pages, 3049 KiB

Open AccessFeature PaperArticle

Design and Characterization of a Screw Extrusion Hot-End for Fused Deposition Modeling

by Tim Feuerbach and Markus Thommes

Molecules 2021, 26(3), 590; https://doi.org/10.3390/molecules26030590 - 23 Jan 2021

Cited by 8 | Viewed by 2110

Abstract

The filament is the most widespread feedstock material form used for fused deposition modeling printers. Filaments must be manufactured with tight dimensional tolerances, both to be processable in the hot-end and to obtain printed objects of high quality. The ability to successfully feed the filament into the printer is also related to the mechanical properties of the filament, which are often insufficient for pharmaceutically relevant excipients. In the scope of this work, an 8 mm single screw hot-end was designed and characterized, which allows direct printing of materials from their powder form and does not require an intermediate filament. The capability of the hot-end to increase the range of applicable excipients to fused deposition modeling was demonstrated by processing and printing several excipients that are not suitable for fused deposition modeling in their filament forms, such as ethylene vinyl acetate and poly(1-vinylpyrrolidone-co-vinyl acetate). The conveying characteristic of the screw was investigated experimentally with all materials and was in agreement with an established model from literature. The complete design information, such as the screw geometry and the hot-end dimensions, is provided in this work. Full article

(This article belongs to the Special Issue 3D Printing for Chemical, Pharmaceutical, and Biological Applications)

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21 pages, 9439 KiB

Open AccessArticle

Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading

by Gordana Stanojević, Djordje Medarević, Ivana Adamov, Nikola Pešić, Jovana Kovačević and Svetlana Ibrić

Molecules 2021, 26(1), 111; https://doi.org/10.3390/molecules26010111 - 29 Dec 2020

Cited by 28 | Viewed by 3376

Abstract

Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers. Full article

(This article belongs to the Special Issue 3D Printing for Chemical, Pharmaceutical, and Biological Applications)

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Review

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30 pages, 2736 KiB

Open AccessReview

3D-Printing of Drug-Eluting Implants: An Overview of the Current Developments Described in the Literature

by Vanessa Domsta and Anne Seidlitz

Molecules 2021, 26(13), 4066; https://doi.org/10.3390/molecules26134066 - 2 Jul 2021

Cited by 45 | Viewed by 5566

Abstract

The usage of 3D-printing for drug-eluting implants combines the advantages of a targeted local drug therapy over longer periods of time at the precise location of the disease with a manufacturing technique that easily allows modifications of the implant shape to comply with the individual needs of each patient. Research until now has been focused on several aspects of this topic such as 3D-printing with different materials or printing techniques to achieve implants with different shapes, mechanical properties or release profiles. This review is intended to provide an overview of the developments currently described in the literature. The topic is very multifaceted and several of the investigated aspects are not related to just one type of application. Consequently, this overview deals with the topic of 3D-printed drug-eluting implants in the application fields of stents and catheters, gynecological devices, devices for bone treatment and surgical screws, antitumoral devices and surgical meshes, as well as other devices with either simple or complex geometry. Overall, the current findings highlight the great potential of the manufacturing of drug-eluting implants via 3D-printing technology for advanced individualized medicine despite remaining challenges such as the regulatory approval of individualized implants. Full article

(This article belongs to the Special Issue 3D Printing for Chemical, Pharmaceutical, and Biological Applications)

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