Development and evaluation of pharmaceutical 3D printability for hot melt extruded cellulose-based filaments

Zhang, Jiaxiang; Xu, Pengchong; Vo, Anh; Bandari, Suresh; Yang, Fengyuan; Dürig, Thomas; Repka, Michael A.

doi:10.1016/j.jddst.2019.04.043

Cited by 65 publications

(44 citation statements)

References 23 publications

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“…Similar results were observed in the current study. In the earlier study, filaments fabricated using HPC EF and HPC HF grades with 30% paracetamol were not suitable for FDM 3D printing [32]. The filaments produced using both HPC EF and HPC HF were too soft.…”

Section: Filament Preparation and Characterizationmentioning

confidence: 94%

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

2020

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This study was performed to develop novel core-shell gastroretentive floating pulsatile drug delivery systems using a hot-melt extrusion-paired fused deposition modeling (FDM) 3D printing and direct compression method. Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC)-based filaments were fabricated using hot-melt extrusion technology and were utilized as feedstock material for printing shells in FDM 3D printing. The directly compressed theophylline tablet was used as the core. The tablet shell to form pulsatile floating dosage forms with different geometries (shell thickness: 0.8, 1.2, 1.6, and 2.0 mm; wall thickness: 0, 0.8, and 1.6 mm; and % infill density: 50, 75, and 100) were designed, printed, and evaluated. All core-shell tablets floated without any lag time and exhibited good floating behavior throughout the dissolution study. The lag time for the pulsatile release of the drug was 30 min to 6 h. The proportion of ethyl cellulose in the filament composition had a significant (p < 0.05) effect on the lag time. The formulation (2 mm shell thickness, 1.6 mm wall thickness, 100% infill density, 0.5% EC) with the desired lag time of 6 h was selected as an optimized formulation. Thus, FDM 3D printing is a potential technique for the development of complex customized drug delivery systems for personalized pharmacotherapy.

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Section: Filament Preparation and Characterizationmentioning

confidence: 94%

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

2020

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“…Flexibility and brittleness properties of the manufactured filaments were evaluated along with ‘Tough PLA’ and ‘Natural PVA’ filaments as the reference material to represent the printability of the filaments [ 33 ]. For flexibility and brittleness analysis, extruded filament samples from each batch were collected and cut into 30 mm in length.…”

Section: Methodsmentioning

confidence: 99%

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

et al. 2020

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This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

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“…Recently, these cellulose-based polymers were investigated in a work by Zhang et al [ 86 ], which provided a deeper knowledge about their properties and respective influence on release profile of the incorporated drugs. In this study, researchers developed a standard guide that assists the development of suitable 3D-printing filaments, based on their suitability for processing.…”

Section: Polymers Used In Hot-melt Extrusion and Fused Deposition mentioning

confidence: 99%

“…In this study, researchers developed a standard guide that assists the development of suitable 3D-printing filaments, based on their suitability for processing. These data were complemented with the physico-chemical and mechanical properties characterization, using the Repka-Zhang model [ 86 ]. This study tested both pure polymeric formulations (HPC EF, HPC HF, HPMC E5, HPMC K100M, HPMCAS LG, HPMCAS HG, and EC N14) and drug-based polymeric preparations (30% w/w acetaminophen as a model) were blended.…”

Section: Polymers Used In Hot-melt Extrusion and Fused Deposition mentioning

confidence: 99%

“…The addition of the model drug affected positively the extrudability of physical mixtures by the reduction of torque, die pressure and temperature required for the extrusion process. This effect was potentially associated with the miscibility between acetaminophen and cellulose-based polymers, which also revealed a crucial role for the drug release modulation [ 86 ]. Among all polymers tested, no issues during the printing process were reported for the formulations with HPMC, and therefore, these polymeric matrices were considered as the best option for FDM 3D-printing technology.…”

Section: Polymers Used In Hot-melt Extrusion and Fused Deposition mentioning

confidence: 99%

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Polymer Selection for Hot-Melt Extrusion Coupled to Fused Deposition Modelling in Pharmaceutics

et al. 2020

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Three-dimensional (3D) printing offers the greatest potential to revolutionize the future of pharmaceutical manufacturing by overcoming challenges of conventional pharmaceutical operations and focusing design and production of dosage forms on the patient’s needs. Of the many technologies available, fusion deposition modelling (FDM) is considered of the lowest cost and higher reproducibility and accessibility, offering clear advantages in drug delivery. FDM requires in-house production of filaments of drug-containing thermoplastic polymers by hot-melt extrusion (HME), and the prospect of connecting the two technologies has been under investigation. The ability to integrate HME and FDM and predict and tailor the filaments’ properties will extend the range of printable polymers/formulations. Hence, this work revises the properties of the most common pharmaceutical-grade polymers used and their effect on extrudability, printability, and printing outcome, providing suitable processing windows for different raw materials. As a result, formulation selection will be more straightforward (considering the characteristics of drug and desired dosage form or release profile) and the processes setup will be more expedite (avoiding or mitigating typical processing issues), thus guaranteeing the success of both HME and FDM. Relevant techniques used to characterize filaments and 3D-printed dosage forms as an essential component for the evaluation of the quality output are also presented.

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Development and evaluation of pharmaceutical 3D printability for hot melt extruded cellulose-based filaments

Cited by 65 publications

References 23 publications

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Polymer Selection for Hot-Melt Extrusion Coupled to Fused Deposition Modelling in Pharmaceutics

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