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Investigations on additive manufacturing for the production of personalised dosage forms of low-dose and thermolabile drugs

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dc.contributor.advisor Walker, Gavin M.
dc.contributor.advisor Croker, Denise M.
dc.contributor.author Kollamaram, Gayathri
dc.date.accessioned 2019-02-13T15:14:00Z
dc.date.available 2019-02-13T15:14:00Z
dc.date.issued 2018
dc.identifier.uri http://hdl.handle.net/10344/7589
dc.description peer-reviewed en_US
dc.description.abstract This thesis reports investigations on Additive Manufacturing (AM) techniques, namely valvejet technology and fused deposition modelling for the production of personalised dosage forms of low dose and low-melting drugs. Inkjet printing has been examined by several research groups for its potential to dispense pharmacological agents into final products, ranging from solid oral dosage forms to functionalized medical devices. However, the thermal and piezoelectric print heads reported in these investigations are best suited to printing solution and nano-suspension inks with particle sizes, solvents and rheological parameters in a narrow range specified by their manufacturers. In the work presented here, we examined a more robust valvejet (‘electromagnetic’) technology which allows coarse and viscous micro-suspensions to be dispensed with high accuracy and precision. More than 40% of newly discovered drugs and an estimated 90% of pipeline drugs are poorly soluble, so there is a clear need for robust printing methods, suitable for printing coarse suspensions. Paracetamol and indomethacin were selected to demonstrate the feasibility of printing soluble and poorly soluble APIs in the form of solution and suspension inks respectively. Valvejet technology has been investigated as a means of depositing solutions with a broader range of viscosity and suspensions with average particle sizes exceeding 2 μm. Printed samples were characterised for their morphology, chemical and solid-sate properties of the active ingredient and content uniformity and mechanical robustness of the coatings. Results from this investigation were used to develop a fixed dose combination of pharmacologically relevant fixed dose combination of ramipril and glimepiride. Also, valvejet technology (being devoid of temperature and stress elements often associated with most additive manufacturing techniques) has been demonstrated to be a promising alternative for producing personalised drug products of drugs that are susceptible to processing conditions. Fused deposition modeling (FDM) is the most commonly investigated of the additive manufacturing techniques to produce drug products and is well suited for the production of high-dose dosage forms. Higher temperatures associated with FDM is the major limiting factor in application of this technique for lower-melting drugs. Kollidon VA64 and Kollidon 12PF, immediate release polymers and PEG 1500 as the primary plasticizer have been investigated to lower the FDM temperature to <100 °C. Ramipril a thermolabile drug with a low melting point 109 °C has been chosen as model drug, the filaments of which were produced using Kollidon VA64 and Kollidon 12PF and was printed at 90 °C- the lowest temperature reported until this work was published and is the lowest melting point drug investigated to date by FDM printing. Developing a library of polymer and excipient combinations that are suited for FDM printing at lower temperatures deserves further investigation. en_US
dc.language.iso eng en_US
dc.publisher University of Limerick en_US
dc.relation 13IA1980 en_US
dc.subject Additive Manufacturing (AM) techniques en_US
dc.subject inkjet printing en_US
dc.subject drugs en_US
dc.title Investigations on additive manufacturing for the production of personalised dosage forms of low-dose and thermolabile drugs en_US
dc.type info:eu-repo/semantics/doctoralThesis en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.type.supercollection ul_theses_dissertations en_US
dc.contributor.sponsor SFI en_US
dc.relation.projectid 13/IA/1980 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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