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      Additive Manufacturing of Personalized Pharmaceutical Dosage Forms via Stereolithography

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          Abstract

          The introduction of three-dimensional printing (3DP) has created exciting possibilities for the fabrication of dosage forms, paving the way for personalized medicine. In this study, oral dosage forms of two drug concentrations, namely 2.50% and 5.00%, were fabricated via stereolithography (SLA) using a novel photopolymerizable resin formulation based on a monomer mixture that, to date, has not been reported in the literature, with paracetamol and aspirin selected as model drugs. In order to produce the dosage forms, the ratio of poly(ethylene glycol) diacrylate (PEGDA) to poly(caprolactone) triol was varied with diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure TPO) utilized as the photoinitiator. The fabrication of 28 dosages in one print process was possible and the printed dosage forms were characterized for their drug release properties. It was established that both drugs displayed a sustained release over a 24-h period. The physical properties were also investigated, illustrating that SLA affords accurate printing of dosages with some statistically significant differences observed from the targeted dimensional range, indicating an area for future process improvement. The work presented in this paper demonstrates that SLA has the ability to produce small, individualized batches which may be tailored to meet patients’ specific needs or provide for the localized production of pharmaceutical dosage forms.

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          Polymers for 3D Printing and Customized Additive Manufacturing

          Additive manufacturing (AM) alias 3D printing translates computer-aided design (CAD) virtual 3D models into physical objects. By digital slicing of CAD, 3D scan, or tomography data, AM builds objects layer by layer without the need for molds or machining. AM enables decentralized fabrication of customized objects on demand by exploiting digital information storage and retrieval via the Internet. The ongoing transition from rapid prototyping to rapid manufacturing prompts new challenges for mechanical engineers and materials scientists alike. Because polymers are by far the most utilized class of materials for AM, this Review focuses on polymer processing and the development of polymers and advanced polymer systems specifically for AM. AM techniques covered include vat photopolymerization (stereolithography), powder bed fusion (SLS), material and binder jetting (inkjet and aerosol 3D printing), sheet lamination (LOM), extrusion (FDM, 3D dispensing, 3D fiber deposition, and 3D plotting), and 3D bioprinting. The range of polymers used in AM encompasses thermoplastics, thermosets, elastomers, hydrogels, functional polymers, polymer blends, composites, and biological systems. Aspects of polymer design, additives, and processing parameters as they relate to enhancing build speed and improving accuracy, functionality, surface finish, stability, mechanical properties, and porosity are addressed. Selected applications demonstrate how polymer-based AM is being exploited in lightweight engineering, architecture, food processing, optics, energy technology, dentistry, drug delivery, and personalized medicine. Unparalleled by metals and ceramics, polymer-based AM plays a key role in the emerging AM of advanced multifunctional and multimaterial systems including living biological systems as well as life-like synthetic systems.
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            Evaluation of 3D printing and its potential impact on biotechnology and the chemical sciences.

            Nearing 30 years since its introduction, 3D printing technology is set to revolutionize research and teaching laboratories. This feature encompasses the history of 3D printing, reviews various printing methods, and presents current applications. The authors offer an appraisal of the future direction and impact this technology will have on laboratory settings as 3D printers become more accessible.
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              A new chapter in pharmaceutical manufacturing: 3D-printed drug products.

              FDA recently approved a 3D-printed drug product in August 2015, which is indicative of a new chapter for pharmaceutical manufacturing. This review article summarizes progress with 3D printed drug products and discusses process development for solid oral dosage forms. 3D printing is a layer-by-layer process capable of producing 3D drug products from digital designs. Traditional pharmaceutical processes, such as tablet compression, have been used for decades with established regulatory pathways. These processes are well understood, but antiquated in terms of process capability and manufacturing flexibility. 3D printing, as a platform technology, has competitive advantages for complex products, personalized products, and products made on-demand. These advantages create opportunities for improving the safety, efficacy, and accessibility of medicines. Although 3D printing differs from traditional manufacturing processes for solid oral dosage forms, risk-based process development is feasible. This review highlights how product and process understanding can facilitate the development of a control strategy for different 3D printing methods. Overall, the authors believe that the recent approval of a 3D printed drug product will stimulate continual innovation in pharmaceutical manufacturing technology. FDA encourages the development of advanced manufacturing technologies, including 3D-printing, using science- and risk-based approaches.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                03 December 2019
                December 2019
                : 11
                : 12
                : 645
                Affiliations
                [1 ]Materials Research Institute, Athlone Institute of Technology, Dublin Road, Athlone, Co., Westmeath N37 HD68, Ireland; andrewhealy@ 123456research.ait.ie (A.V.H.); e.fuenmayor@ 123456research.ait.ie (E.F.); lgeever@ 123456ait.ie (L.M.G.); chigginbotham@ 123456ait.ie (C.L.H.)
                [2 ]Applied Polymer Technologies Gateway, Athlone Institute of Technology, Dublin Road, Athlone, Co., Westmeath N37 HD68, Ireland; patrickdoran@ 123456ait.ie
                [3 ]Faculty of Engineering and Informatics, Athlone Institute of Technology, Dublin Road, Athlone, Co., Westmeath N37 HD68, Ireland
                Author notes
                [* ]Correspondence: slyons@ 123456ait.ie ; Tel.: +353-(0)90-64-68150
                Author information
                https://orcid.org/0000-0002-9466-5964
                https://orcid.org/0000-0003-1998-070X
                Article
                pharmaceutics-11-00645
                10.3390/pharmaceutics11120645
                6955879
                31816898
                9ecb1fdc-8da9-41ee-9177-59432082892b
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 October 2019
                : 28 November 2019
                Categories
                Article

                stereolithography,three-dimensional printing,additive manufacturing,personalized medicine,3d printed oral dosage forms,drug delivery,sustained drug release tablets,photopolymerization,paracetamol (acetaminophen),aspirin (acetylsalicylic acid)

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