Boyd, Peter

Devlin, Brid

Malcolm, Robert

McCoy, Clare F.

Murphy, Diarmaid

Welsh, Nicole

Background: Droplet deposition modelling (DDM) is a form of 3D printing that fuses droplets of molten polymer to create each layer, providing exquisite levels of control over an object‘s design and morphology. Such manipulation allows properties including density, geometry and surface area to be manipulated in ways that have been unthinkable using conventional thermoplastic processing techniques. Here we utilise the DDM process and compare this to injection moulding to produce dapivirine (DPV) loaded vaginal rings using a pharmaceutically relevant, life science grade thermoplastic polyurethane.Methods: Vaginal rings (54.0 mm outer diameter, 4.0 mm cross sectional diameter) were fabricated by injection molding or Arburg Plastic Freeforming - a proprietary DDM process, using a hydrophobic TPU loaded with 10% w/w dapivirine. Using the DDM process, rings of 100, 50 and 10% matrix density were produced. Rings were evaluated for in vitro drug release over 29 days in an aqueous release media and assessed for thermal characteristics. Results: Daily DPV release from all ring designs ranged between 387 - 8666 μg (Day 1) and 193 - 992 μg on Day 29. DDM printed VRs with 10% infill density (68 mg DPV load) exhibited a seven fold increase in DPV release rate compared to injection molded rings containing 190 mg DPV. For DDM printed rings, there was very significant correlation between decreasing ring density and increasing DPV release rate as a percentage of total drug loading. Thermal analysis showed that the DPV melt endotherm was absent from TPU + 10% w/w DPV, suggesting that DPV was fully solubilised within the TPU at the experimental conditions.Conclusions: DDM printing on an Arburg Freeformer has been shown to create vaginal rings with a range of densities and has provided a new potential to either increase the release rate of poorly water soluble compounds or reduce the loading required to maintain a desired release rate

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Density Mediated Drug Release From Dapivirine Vaginal RingsProduced by Additive ManufacturingMalcolm, R., Welsh, N., McCoy, C. F., Murphy, D., Devlin, B., & Boyd, P. (2018). Density Mediated DrugRelease From Dapivirine Vaginal Rings Produced by Additive Manufacturing. P09.19. Poster session presentedat HIV Research for Prevention 2018, Madrid, Spain.Document Version:Publisher's PDF, also known as Version of recordQueen's University Belfast - Research Portal:Link to publication record in Queen's University Belfast Research PortalPublisher rightsCopyright 2018 HIVR4P. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable termsof use of the publisherGeneral rightsCopyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or othercopyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associatedwith these rights.Take down policyThe Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made toensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws. If you discover content in theResearch Portal that you believe breaches copyright or violates any law, please contact openaccess@qub.ac.uk.Download date:10. Nov. 2018Density mediated drug release from dapivirine vaginal rings produced by additive manufacturingBackgroundObjectivesMethodsDroplet deposition modelling (DDM) is a form of 3D printing thatfuses droplets of molten polymer to create each layer, providingexquisite levels of control over an object’s design and morphology.Such manipulation allows properties including density, geometry andsurface area to be manipulated in ways that have been unthinkableusing conventional thermoplastic processing techniques. Here weutilise the DDM process and compare this to injection moulding (IM)to produce dapivirine (DPV) loaded vaginal rings using apharmaceutically relevant, life science grade thermoplasticpolyurethane.Identify grades of TPU which are compatible with both additivemanufacturing (DDM) and traditional manufacturing processes (IM).• Thermoplastic polymers should have ≤2% weight loss atprocessing temperature as assessed by TGA.Compound filament with 10% w/w DPV and pelletise to producepellets ~2.0 mm.Compare drug delivery and other physiochemical properties ofvaginal drug delivery devices fabricated by additive manufacturing(DDM) against conventional manufacturing techniques (IM).Vaginal rings (54.0 mm outer diameter, 4.0 mm cross sectionaldiameter) were fabricated by injection molding or Arburg PlasticFreeforming – a proprietary DDM process, using a hydrophobic TPU(T87 or T60) loaded with 10% w/w dapivirine. Using the DDMprocess, rings of 100, 50 and 10% matrix density were produced.Rings were evaluated for in vitro drug release over 29 days in anaqueous release media and assessed for thermal characteristics.ResultsDDM printing on an Arburg Freeformer has provided a new potential to either increase the release rate of poorly water soluble compounds or reduce the loading required to maintain a desired release rate.VRs with an infill density of 100% manufactured by IM and DDM released up to 4 and 10% of their total DPV loading, while rings with an infill density of 50 or 10% (DDM) released up to 56 and 79% of their total DPV loading after 29 days.Key pointsDDM printing on an Arburg Freeformer has been shown to create vaginal rings with a range of densities.Nicole Welsh1, Clare F. McCoy1, Diarmaid J. Murphy1, R. Karl Malcolm1, Brid Devlin2, Peter Boyd11School of Pharmacy,Queen’s University Belfast,Belfast BT9 7BL, UKE: k.malcolm@qub.ac.ukFig. 2: DSC thermal trace for model drug (DPV), DPV loaded (10% w/w) T87 and T60 filament (n=3, representative data shown). Samples were heated from either -90°C or -50°C to 250°C at a rate of 20°C min-1.1 2 32International Partnership for MicrobicidesSilver SpringMaryland 20910E: bdevlin@ipmglobal.org-100 -50 0 50 100 150 200 2502.5 W/g20.0 W/gExo upDPVT60 10% DPVT87 10% DPVTemperature (°C)Heat Flow (W/g)A1Fig. 1: Diagram of Arburg Freeformer and internal components.Fig. 4: Digital images showing the base of a quarter of T87-DPV VRs (outer diameter 54.00 mm,cross-sectional diameter 4.00 mm) fabricated by droplet deposition modelling with an infill density of(1) 100%, (2) 50% and (3) 10%.1A21 2 3Fig. 3: (A) Daily (Mean ± SD, n=6) and (B) Cumulative release (n=6) of DPV from T87-DPV vaginal rings (outer diameter 54.00 mm, cross-sectional diameter 4.00 mm, fabricated by injection molding (IM) or droplet deposition modelling (DDM) with densities of 10% (R10), 50% (R50) or 100% (R100). In-vitro release was performed in a 0.2% tween solution.B5 10 15 20 25 30020406080Time	(days)Cumula7ve	DPV	Release	(mg)BAPF R10APF R50APF R100IM R100B25 10 15 20 25 30020406080100Time	(days)Cumula7ve	DPV	Release	(%)BDDM R10DDM R50DDM R100IM R10010%densityIM62 mgtotal DPV45 mg of drug released60 mg of drug released16 mg of drug released5 mg of drug released50%density111 mgtotal DPV100%density118 mgtotal DPV190 mgtotal DPVFig. 5: Cumulative release plotted as a percentage of the total drug loading in each of the vaginalring types (n=6) of DPV from T87-DPV vaginal rings (outer diameter 54.00 mm, cross-sectionaldiameter 4.00 mm, fabricated by injection molding (IM) or droplet deposition modelling (DDM) withdensities of 10%, 50% or 100%. In-vitro release was performed in a 0.2% tween solution. The ringphotographs indicate the density and total drug loading (mg) for each type of ring.Table 1: Dimensional analysis of DDM printed VRs (n=6) manufactured using T87-DPV or T60- DPV

Density Mediated Drug Release From Dapivirine Vaginal Rings Produced by Additive Manufacturing

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Density Mediated Drug Release From Dapivirine Vaginal Rings Produced by Additive Manufacturing

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