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Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs

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Show simple item record Kollamaram, Gayathri Croker, Denise M. Walker, Gavin M. Goyanes, Alvaro Basit, Abdul W. Gaisford, Simon 2018-05-14T11:34:17Z 2018
dc.description peer-reviewed en_US
dc.description.abstract Fused deposition modelling (FDM) is the most commonly investigated 3D printing technology for the manufacture of personalized medicines, however, the high temperatures used in the process limit its wider application. The objective of this study was to print low-melting and thermolabile drugs by reducing the FDM printing temperature. Two immediate release polymers, Kollidon VA64 and Kollidon 12PF were investigated as potential candidates for low-temperature FDM printing. Ramipril was used as the model low melting temperature drug (109 °C); to the authors’ knowledge this is the lowest melting point drug investigated to date by FDM printing. Filaments loaded with 3% drug were obtained by hot melt extrusion at 70 °C and ramipril printlets with a dose equivalent of 8.8 mg were printed at 90 °C. HPLC analysis confirmed that the drug was stable with no signs of degradation and dissolution studies revealed that drug release from the printlets reached 100% within 20–30 min. Variable temperature Raman and solid state nuclear magnetic resonance (SSNMR) spectroscopy techniques were used to evaluate drug stability over the processing temperature range. These data indicated that ramipril did not undergo degradation below its melting point (which is above the processing temperature range: 70–90 °C) but it was transformed into the impurity diketopiperazine upon exposure to temperatures higher than its melting point. The use of the excipients Kollidon VA64 and Kollidon 12PF in FDM was further validated by printing with the drug 4-aminosalicylic acid (4-ASA), which in previous work was reported to undergo degradation in FDM printing, but here it was found to be stable. This work demonstrates that the selection and use of new excipients can overcome one of the major disadvantages in FDM printing, drug degradation due to thermal heating, making this technology suitable for drugs with lower melting temperatures. en_US
dc.language.iso eng en_US
dc.publisher University of Limerick en_US
dc.relation.ispartofseries International Journal of Pharmaceutics;545 (1-2), pp. 144-152
dc.rights This is the author’s version of a work that was accepted for publication in International Journal of Pharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in International Journal of Pharmaceutics, 2018, 545 (1-2), pp. 144-152, en_US
dc.subject three-dimensional printing en_US
dc.subject additive manufacturing en_US
dc.subject material extrusion en_US
dc.subject fused filament fabrication en_US
dc.subject material extrusion en_US
dc.subject fused deposition modelling en_US
dc.subject personalised medicines en_US
dc.subject printing pharmaceuticals en_US
dc.title Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1016/j.ijpharm.2018.04.055
dc.contributor.sponsor SFI en_US
dc.contributor.sponsor Programme for Research in Third Level Institutions, Cycle 5 en_US
dc.relation.projectid 12/RC/2275 en_US
dc.relation.projectid 13/IA/1980 en_US
dc.relation.projectid 12/RI/2345 en_US 2019-07-10
dc.embargo.terms 2019-07-10 en_US
dc.rights.accessrights info:eu-repo/semantics/embargoedAccess en_US

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