Roadmap to 3D-Printed Oral Pharmaceutical Dosage Forms: Feedstock Filament Properties and Characterization for Fused Deposition Modeling

Aho, Johanna; Boetker, Johan; Genina, Natalja; Edinger, Magnus; Arnfast, Lærke

doi:10.1016/j.xphs.2018.11.012

Cited by 114 publications

(60 citation statements)

References 70 publications

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“…Consequently, the material amount which passes the die varies and, with it, the diameter. To what extent these fluctuations occur is highly dependent on the viscoelastic behavior of the used material and die swell [ 25 ]. In this study, an impact of inhomogeneous powder feeding could be excluded (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Hot-Melt Extrusion Process Fluctuations and Their Impact on Critical Quality Attributes of Filaments and 3D-Printed Dosage Forms

2020

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Fused deposition modeling (FDMTM) is a 3D-printing technology of rising interest for the manufacturing of customizable solid dosage forms. The coupling of hot-melt extrusion with FDMTM is favored to allow the production of pharma-grade filaments for the printing of medicines. Filament diameter consistency is a quality of great importance to ensure printability and content uniformity of 3D-printed drug delivery systems. A systematical process analysis referring to filament diameter variations has not been described in the literature. The presented study aimed at a process setup optimization and rational process analysis for filament fabrication related to influencing parameters on diameter inhomogeneity. In addition, the impact of diameter variation on the critical quality attributes of filaments (mechanical properties) and uniformity of mass of printed drug-free dosage forms was investigated. Process optimization by implementing a winder with a special haul-off unit was necessary to obtain reliable filament diameters. Subsequently, the optimized setup was used for conduction of rational extrusion analysis. The results revealed that an increased screw speed led to diameter fluctuations with a decisive influence on the mechanical resilience of filaments and mass uniformity of printed dosage forms. The specific feed load was identified as a key parameter for filament diameter consistency.

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Section: Resultsmentioning

confidence: 99%

Hot-Melt Extrusion Process Fluctuations and Their Impact on Critical Quality Attributes of Filaments and 3D-Printed Dosage Forms

2020

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“…A similar observation was cited by Aho et al and was attributed to the presence of solid fillers decreasing the elasticity ratio between the normal force and shear stress. Increasing particle concentration reduced die swell during extrusion [29].…”

Section: Accepted Manuscriptmentioning

confidence: 95%

Development of a hot-melt extrusion (HME) process to produce drug loaded Affinisol™ 15LV filaments for fused filament fabrication (FFF) 3D printing

Prasad

Islam

Goodwin

et al. 2019

Additive Manufacturing

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The aim of the present work was to develop a pilot scale process to produce drug-loaded filaments for 3D printing of oral solid dose forms by fused filament fabrication (FFF). Using hot melt extrusion, a viable operating space and understanding of processing limits were established using a hydrophilic polymer (hydroxypropyl methylcellulose (HPMC)-Affinisol™ LV15). This was then extended to formulate paracetamol (PCM) loaded Affinisol™ 15LV filaments across a wide range of compositions (5-50 wt% drug). From the process development work, challenges in achieving a pilot scale process for filament production for pharmaceutical applications have been highlighted. 3D printing trials across the range of compositions demonstrated limitations concerning the ability to print successfully across all compositions. Results from characterisation techniques including thermal and mechanical testing when applied to the formulated filaments indicated that these techniques are a useful predictive measure for assessing the ability to print a given formulation via filament methods. Oral solid dosage forms of variable surface area to mass ratios printed from suitable filament 2 compositions demonstrated the ability to modify the release rates of drug for fixed formulations across substantial timescales.

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“…This reflects variations in disc thickness at the level of a single disc for all print volumes in this study. Since filament brittleness prevented automated feeding, this dispensing imprecision likely signals a sensitivity to manual feeding rates (38,39). However, mass deviations revealing over-extrusion and under-extrusion from the FDM nozzle were encountered previously, despite automated feeding, at both larger print volumes (74 to 468 mm 3 ) (21) and smaller print volumes (20).…”

Section: Resultsmentioning

confidence: 99%

“…This, in turn, relies upon a filament feedstock with high diameter tolerances and either filament feeding mechanisms adaptable to a wide range of filament properties or restriction to use of suitable materials or optimisation of formulations for the types of feeding mechanisms available. Beyond compatibility with current FDM feeding mechanisms, filaments for FDM are required to simultaneously fulfil a host of thermal, mechanical and rheological properties whilst providing the relevant pharmaceutical function (38).…”

Section: Discussionmentioning

confidence: 99%

High Content Solid Dispersions for Dose Window Extension: A Basis for Design Flexibility in Fused Deposition Modelling

et al. 2019

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PurposeThis study uses high drug content solid dispersions for dose window extension beyond current demonstrations using fused deposition modelling (FDM) to; i) accommodate pharmaceutically relevant doses of drugs of varying potencies at acceptable dosage form sizes and ii) enable enhanced dose flexibility via modular dosage form design concepts.MethodsFDM was used to generate ~0.5 mm thick discs of varying diameter (2–10 mm) from melt-extruded feedstocks based on 10% to 50% w/w felodipine in ethyl cellulose. Drug content was determined by UV spectroscopy and dispensing precision from printed disc mass.ResultsMean felodipine content was within ±5% of target values for all print volumes and compositions including contents as high as ~50% w/w. However, poor dispensing precision was evident at all print volumes.ConclusionsIn pursuit of dose flexibility, this successful demonstration of dose window extension using high content solid dispersions preserves FDM design flexibility by maintaining applicability to drugs of varying potencies. The achieved uniformity of content supports the application of varying content solid dispersions to modular dosage form concepts to enhance dose flexibility. However, poor dispensing precision impedes its utilisation until appropriate compatibility between FDM hardware and materials at varying drug contents can be attained.

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Roadmap to 3D-Printed Oral Pharmaceutical Dosage Forms: Feedstock Filament Properties and Characterization for Fused Deposition Modeling

Cited by 114 publications

References 70 publications

Hot-Melt Extrusion Process Fluctuations and Their Impact on Critical Quality Attributes of Filaments and 3D-Printed Dosage Forms

Hot-Melt Extrusion Process Fluctuations and Their Impact on Critical Quality Attributes of Filaments and 3D-Printed Dosage Forms

Development of a hot-melt extrusion (HME) process to produce drug loaded Affinisol™ 15LV filaments for fused filament fabrication (FFF) 3D printing

High Content Solid Dispersions for Dose Window Extension: A Basis for Design Flexibility in Fused Deposition Modelling

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