A Review of Hot-Melt Extrusion: Process Technology to Pharmaceutical Products

Over the last three decades industrial adaptability has allowed hot-melt extrusion (HME) to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. HME has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and targeted drug delivery resulting in improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). This paper reviews the innumerable benefits of HME, based on a holistic perspective of the equipment, processing technologies to the materials, novel formulation design and developments, and its varied applications in oral drug delivery systems.

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Preparation of monolithic matrices for oral drug delivery using a supercritical fluid assisted hot melt extrusion process

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2006.08.028 ◽

2007 ◽

Vol 329 (1-2) ◽

pp. 62-71 ◽

Cited By ~ 43

Author(s):

J LYONS ◽

M HALLINAN ◽

J KENNEDY ◽

D DEVINE ◽

L GEEVER ◽

...

Keyword(s):

Drug Delivery ◽

Supercritical Fluid ◽

Oral Drug Delivery ◽

Hot Melt Extrusion ◽

Extrusion Process ◽

Oral Drug ◽

Melt Extrusion ◽

Hot Melt

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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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Review on Hot Melt Extrusion Technology and it's Application

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst196653 ◽

2019 ◽

pp. 253-260

Author(s):

Mali A. S. ◽

Gavali K. V. ◽

Choudhari R. G. ◽

Anekar V. P. ◽

Gavhane Y. N.

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Hot Melt Extrusion ◽

Delivery Systems ◽

Taste Masking ◽

Melt Extrusion ◽

Pharmaceutical Ingredients ◽

Pharmaceutical Industries ◽

Extrusion Technology ◽

Hot Melt

The use of hot-melt extrusion (HME) within the pharmaceutical industry is steadily increasing, due to proven its ability to efficiently manufacture novel products. With the use of HME we can increase solubility and bioavailability of the API. HME has proven to be a robust method of producing numerous drug delivery systems like modified, controlled and targeted drug delivery systems. resulting improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). Hot-melt extrusion techniques are pragmatic in the manufacture of a variety of dosage forms and formulations such as granules, pellets, tablets, suppositories, implants, stents, transdermal systems and ophthalmic inserts. In This paper we review about the types of Extruder, solid dispersion and Application of the HME to the pharmaceutical industries.

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A Muco-Adhesive Drug Delivery System for the Enhancement of the Bioavailability of Ondansetron Hydrochloride Using Hot-Melt Extrusion Technology

10.26226/morressier.57d6b2bed462b8028d88d714 ◽

2016 ◽

Author(s):

Nicole Mendonsa

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Hot Melt Extrusion ◽

Melt Extrusion ◽

Ondansetron Hydrochloride ◽

Extrusion Technology ◽

Hot Melt

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The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in Combination with Polymers

Pharmaceutics ◽

10.3390/pharmaceutics13030344 ◽

2021 ◽

Vol 13 (3) ◽

pp. 344

Author(s):

Jong-Hwa Lee ◽

Hyeong Sik Jeong ◽

Jong-Woo Jeong ◽

Tae-Sung Koo ◽

Do-Kyun Kim ◽

...

Keyword(s):

Drug Delivery ◽

Dissolution Rate ◽

Solid Dispersion ◽

Oral Drug Delivery ◽

Amorphous Solid ◽

Drug Dissolution ◽

Oral Drug ◽

Amorphous Solid Dispersion ◽

Screw Speed ◽

Hot Melt

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1–1:4) and barrel temperature (200–240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

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

Pharmaceutics ◽

10.3390/pharmaceutics10040203 ◽

2018 ◽

Vol 10 (4) ◽

pp. 203 ◽

Cited By ~ 63

Author(s):

Deck Tan ◽

Mohammed Maniruzzaman ◽

Ali Nokhodchi

Keyword(s):

3D Printing ◽

Hot Melt Extrusion ◽

Pharmaceutical Products ◽

Fused Deposition Modelling ◽

Melt Extrusion ◽

3D Object ◽

3D Printing Technology ◽

Fused Deposition ◽

Pharmaceutical Applications ◽

Hot Melt

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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