Advanced Pharmaceutical Applications of Hot-Melt Extrusion Coupled with Fused Deposition Modelling (FDM) 3D Printing for Personalised Drug Delivery

Three-dimensional printing, also known as additive manufacturing, is a fabrication process whereby a 3D object is created layer-by-layer by depositing a feedstock material such as thermoplastic polymer. The 3D printing technology has been widely used for rapid prototyping and its interest as a fabrication method has grown significantly across many disciplines. The most common 3D printing technology is called the Fused Deposition Modelling (FDM) which utilises thermoplastic filaments as a starting material, then extrudes the material in sequential layers above its melting temperature to create a 3D object. These filaments can be fabricated using the Hot-Melt Extrusion (HME) technology. The advantage of using HME to manufacture polymer filaments for FDM printing is that a homogenous solid dispersion of two or more pharmaceutical excipients i.e., polymers can be made and a thermostable drug can even be introduced in the filament composition, which is otherwise impractical with any other techniques. By introducing HME techniques for 3D printing filament development can improve the bioavailability and solubility of drugs as well as sustain the drug release for a prolonged period of time. The latter is of particular interest when medical implants are considered via 3D printing. In recent years, there has been increasing interest in implementing a continuous manufacturing method on pharmaceutical products development and manufacture, in order to ensure high quality and efficacy with less batch-to-batch variations of the pharmaceutical products. The HME and FDM technology can be combined into one integrated continuous processing platform. This article reviews the working principle of Hot Melt Extrusion and Fused Deposition Modelling, and how these two technologies can be combined for the use of advanced pharmaceutical applications.

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Development and Optimisation of Novel Polymeric Compositions for Sustained Release Theophylline Caplets (PrintCap) via FDM 3D Printing

Polymers ◽

10.3390/polym12010027 ◽

2019 ◽

Vol 12 (1) ◽

pp. 27 ◽

Cited By ~ 8

Author(s):

Deck Khong Tan ◽

Mohammed Maniruzzaman ◽

Ali Nokhodchi

Keyword(s):

Drug Delivery ◽

3D Printing ◽

Sustained Release ◽

Hot Melt Extrusion ◽

Pharmaceutical Products ◽

Successful Implementation ◽

Melt Extrusion ◽

Fused Deposition ◽

Continuous Fabrication ◽

Hot Melt

This study reports a thorough investigation combining hot-melt extrusion technology (HME) and a low-cost fused deposition modelling (FDM) 3D printer as a continuous fabrication process for a sustained release drug delivery system. The successful implementation of such an approach presented herein allows local hospitals to manufacture their own medical and pharmaceutical products on-site according to their patients’ needs. This will help save time from waiting for suitable products to be manufactured off-site or using traditional manufacturing processes. The filaments were produced by optimising various compositions of pharmaceutical-grade polymers, such as hydroxypropyl cellulose (HPC), Eudragit® (RL PO), and polyethylene glycol (PEG), whereas theophylline was used as a model thermally stable drug. For the purpose of the study, twin-screw hot-melt extrusion (HME) was implemented from the view that it would result in the formation of solid dispersion of drug in the polymeric carrier matrices by means of high shear mixing inside the heated barrel. Four filament compositions consisting of different ratios of polymers were produced and their properties were assessed. The mechanical characterisation of the filaments revealed quite robust properties of the filaments suitable for FDM 3D printing of caplets (PrintCap), whereas the solid-state analyses conducted via DSC and XRD showed amorphous nature of the crystalline drug dispersed in the polymeric matrices. Moreover, the surface analysis conducted via SEM showed a smooth surface of the produced filaments as well as caplets where no drug crystals were visible. The in vitro drug release study showed a sustained release profile over 10 h where about 80% of the drug was released from the printed dosage forms. This indicates that our optimised 3D printed caplets could be suitable for the development of sustained release on-demand drug delivery systems.

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The Impact of Hot Melt Extrusion and Fused Deposition Modelling 3D Printing on Polyvinylpyrrolidone-Based Matrix

10.26226/morressier.57d6b2bed462b8028d88dd97 ◽

2016 ◽

Author(s):

Tochukwu Okwuosa

Keyword(s):

3D Printing ◽

Hot Melt Extrusion ◽

Fused Deposition Modelling ◽

Melt Extrusion ◽

Fused Deposition ◽

The Impact ◽

Hot Melt

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Hot Melt Extrusion and its Application in 3D Printing of Pharmaceuticals

Current Drug Delivery ◽

10.2174/1567201817999201110193655 ◽

2020 ◽

Vol 17 ◽

Author(s):

Sanjeevani Deshkar ◽

Mrunali Rathi ◽

Shital Zambad ◽

Krishnakant Gandhi

Keyword(s):

3D Printing ◽

Dosage Form ◽

Fused Deposition Modeling ◽

Hot Melt Extrusion ◽

Taste Masking ◽

Melt Extrusion ◽

Fused Deposition ◽

Continuous Pharmaceutical Manufacturing ◽

Solubility Improvement ◽

Hot Melt

Abstract:: Hot melt extrusion (HME) is a continuous pharmaceutical manufacturing process that has been extensively inves-tigated for solubility improvement and taste masking of active pharmaceutical ingredients. Recently, it is being explored for its application in 3D printing. 3D printing of pharmaceuticals allows flexibility of dosage form design, customization of dosage form for personalized therapy and the possibility of complex designs with the inclusion of multiple actives in a sin-gle unit dosage form. Fused deposition modeling (FDM) is a 3D printing technique with a variety of applications in pharma-ceutical dosage form development. FDM process requires a polymer filament as the starting material that can be obtained by hot melt extrusion. Recent reports suggest enormous applications of a combination of hot melt extrusion and FDM technol-ogy in 3D printing of pharmaceuticals and need to be investigated further. This review in detail describes the HME process along with its application in 3D printing. The review also summarizes the published reports on the application of HME cou-pled with 3D printing technology in drug delivery.

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A Low-Cost Method to Prepare Biocompatible Filaments with Enhanced Physico-mechanical Properties for FDM 3D Printing

Current Drug Delivery ◽

10.2174/1567201817999201103195456 ◽

2020 ◽

Vol 18 ◽

Author(s):

Deck Khong Tan ◽

Niko Münzenrieder ◽

Mohammed Maniruzzaman ◽

Ali Nokhodchi

Keyword(s):

3D Printing ◽

Low Cost ◽

Fused Deposition Modelling ◽

Processing Temperature ◽

Melt Extrusion ◽

Screw Extruder ◽

Fused Deposition ◽

Single Screw ◽

Pharmaceutical Applications ◽

Twin Screw

Background: Fused Deposition Modelling (FDM) 3D printing has received much interest as a fabrication method in the medical and pharmaceutical industry due to its accessibility and cost-effectiveness. A low-cost method to produce biocompatible and biodegradable filaments can improve the usability of FDM 3D printing for biomedical applications. Objectives: The feasibility of producing low-cost filaments suitable for FDM 3D printing via single screw and twin-screw hot melt extrusion was explored. Methods: A single-screw extruder and a twin-screw extruder were used to produce biocompatible filaments composed of varying concentrations of polyethylene glycol (PEG) at 10%, 20%, 30% w/w and polylactic acid (PLA) 90%, 80% and 70% w/w, respectively. DSC, TGA and FTIR were employed to investigate the effect of PEG on the PLA filaments. Results: The presence of PEG lowered the processing temperature of the formulation compositions via melt-extrusion, making it suitable for pharmaceutical applications. The use of PEG can lower the melting point of the PLA polymer to 170 °C, hence lowering the printing temperature. PEG can also improve the plasticity of the filaments, as the rupture strain of twinscrew extruded filaments increased up to 10-fold as compared to the commercial filaments. Advanced application of FTIR analysis confirmed the compatibility and miscibility of PEG with PLA. Conclusion: Twin-screw extrusion is more effective in producing a polymeric mixture of filaments as the mixing is more homogenous. The PEG/PLA filament is suitable to be used in 3D printing of medical or pharmaceutical applications such as medical implants, drug delivery systems, or personalised tablets.

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Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics

Pharmaceutics ◽

10.3390/pharmaceutics13091424 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1424

Author(s):

Juliana dos Santos ◽

Guilherme Silveira da Silva ◽

Maiara Callegaro Velho ◽

Ruy Carlos Ruver Beck

Keyword(s):

Drug Delivery ◽

3D Printing ◽

Drug Delivery Systems ◽

Hot Melt Extrusion ◽

Delivery Systems ◽

Melt Extrusion ◽

Swelling Properties ◽

Fused Deposition ◽

Hot Melt ◽

Printing Techniques

Eudragit® polymers are polymethacrylates highly used in pharmaceutics for the development of modified drug delivery systems. They are widely known due to their versatility with regards to chemical composition, solubility, and swelling properties. Moreover, Eudragit polymers are thermoplastic, and their use has been boosted in some production processes, such as hot melt extrusion (HME) and fused deposition modelling 3D printing, among other 3D printing techniques. Therefore, this review covers the studies using Eudragit polymers in the development of drug delivery systems produced by HME and 3D printing techniques over the last 10 years. Eudragit E has been the most used among them, mostly to formulate immediate release systems or as a taste-masker agent. On the other hand, Eudragit RS and Eudragit L100-55 have mainly been used to produce controlled and delayed release systems, respectively. The use of Eudragit polymers in these processes has frequently been devoted to producing solid dispersions and/or to prepare filaments to be 3D printed in different dosage forms. In this review, we highlight the countless possibilities offered by Eudragit polymers in HME and 3D printing, whether alone or in blends, discussing their prominence in the development of innovative modified drug release systems.

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Hot melt extrusion paired fused deposition modeling 3D printing to develop hydroxypropyl cellulose based floating tablets of cinnarizine

Carbohydrate Polymers ◽

10.1016/j.carbpol.2020.116519 ◽

2020 ◽

Vol 246 ◽

pp. 116519 ◽

Cited By ~ 6

Author(s):

Anh Q. Vo ◽

Jiaxiang Zhang ◽

Dinesh Nyavanandi ◽

Suresh Bandari ◽

Michael A. Repka

Keyword(s):

3D Printing ◽

Fused Deposition Modeling ◽

Hot Melt Extrusion ◽

Hydroxypropyl Cellulose ◽

Melt Extrusion ◽

Floating Tablets ◽

Fused Deposition ◽

Deposition Modeling ◽

Hot Melt

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

Pharmaceutics ◽

10.3390/pharmaceutics12010052 ◽

2020 ◽

Vol 12 (1) ◽

pp. 52 ◽

Cited By ~ 19

Author(s):

Nagi Reddy Dumpa ◽

Suresh Bandari ◽

Michael A. Repka

Keyword(s):

Drug Delivery ◽

3D Printing ◽

Fused Deposition Modeling ◽

Lag Time ◽

Hot Melt Extrusion ◽

Melt Extrusion ◽

Fused Deposition ◽

Deposition Modeling ◽

Pulsatile Drug Delivery ◽

Hot Melt

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

Pharmaceutics ◽

10.3390/pharmaceutics12090795 ◽

2020 ◽

Vol 12 (9) ◽

pp. 795 ◽

Cited By ~ 2

Author(s):

Gabriela G. Pereira ◽

Sara Figueiredo ◽

Ana Isabel Fernandes ◽

João F. Pinto

Keyword(s):

Raw Materials ◽

Three Dimensional ◽

Hot Melt Extrusion ◽

Dosage Forms ◽

Fused Deposition Modelling ◽

Melt Extrusion ◽

Fused Deposition ◽

The Many ◽

House Production ◽

Hot Melt

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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