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      Application of three-dimensional printing for colon targeted drug delivery systems

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          Abstract

          Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

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          Most cited references48

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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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            Effect of geometry on drug release from 3D printed tablets

            The aim of this work was to explore the feasibility of combining hot melt extrusion (HME) with 3D printing (3DP) technology, with a view to producing different shaped tablets which would be otherwise difficult to produce using traditional methods. A filament extruder was used to obtain approx. 4% paracetamol loaded filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3DP. Five different tablet geometries were successfully 3D-printed-cube, pyramid, cylinder, sphere and torus. The printing process did not affect the stability of the drug. Drug release from the tablets was not dependent on the surface area but instead on surface area to volume ratio, indicating the influence that geometrical shape has on drug release. An erosion-mediated process controlled drug release. This work has demonstrated the potential of 3DP to manufacture tablet shapes of different geometries, many of which would be challenging to manufacture by powder compaction.
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              Fused-filament 3D printing (3DP) for fabrication of tablets

              The use of fused-filament 3D printing (FF 3DP) to fabricate individual tablets is demonstrated. The technology permits the manufacture of tablets containing drug doses tailored to individual patients, or to fabrication of tablets with specific drug-release profiles. Commercially produced polyvinyl alcohol (PVA) filament was loaded with a model drug (fluorescein) by swelling of the polymer in ethanolic drug solution. A final drug-loading of 0.29% w/w was achieved. Tablets of PVA/fluorescein (10 mm diameter) were printed using a 3D printer. It was found that changing the degree of infill percentage in the printer software varied the weight and volume of the printed tablets. The tablets were mechanically strong and no significant thermal degradation of the active occurred during printing. Dissolution tests were conducted in modified Hank's buffer. The results showed release profiles were dependent on the infill percentage used to print the tablet. The study indicates that FF 3DP has the potential to offer a new solution for fabricating personalized-dose medicines or unit dosage forms with controlled-release profiles. In addition, the low cost of FDM printers means the paradigm of extemporaneous or point-of-use manufacture of personalized-dose tablets is both feasible and attainable.
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                Author and article information

                Journal
                Int J Pharm Investig
                Int J Pharm Investig
                IJPI
                International Journal of Pharmaceutical Investigation
                Medknow Publications & Media Pvt Ltd (India )
                2230-973X
                2230-9713
                Apr-Jun 2017
                : 7
                : 2
                : 47-59
                Affiliations
                [1]Unit of Clinical Pharmacology, Luigi Sacco University Hospital, University of Milan, Milan, Italy
                [1 ]School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Co. Londonderry, United Kingdom
                [2 ]UCL School of Pharmacy, London, England, United Kingdom
                Author notes
                Address for correspondence: Dr. Murtaza M. Tambuwala, Saad Centre for Pharmacy and Diabetes, School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, BT52 1SA, Northern Ireland, United Kingdom. E-mail: m.tambuwala@ 123456ulster.ac.uk
                Article
                IJPI-7-47
                10.4103/jphi.JPHI_32_17
                5553264
                28929046
                af17c469-71d8-46ca-b00e-6f39517ed5b0
                Copyright: © 2017 International Journal of Pharmaceutical Investigation

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Categories
                Review Article

                Pharmacology & Pharmaceutical medicine
                colitis,colon drug delivery,personalized medicine,three-dimensional printing

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