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Journal ArticleDOI

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

01 Feb 2016-Aaps Pharmscitech (Springer US)-Vol. 17, Iss: 1, pp 20-42
TL;DR: This review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.
Abstract: Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

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Citations
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Journal ArticleDOI
TL;DR: This review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of amorphous solid dispersion systems and potential advantage of polymers as inert, hydrophilic, pharmaceutical carrier matrices.

680 citations

Journal ArticleDOI
TL;DR: 3D-printed tablets showed better extended drug release rates than the directly compressed tablets did and were clearly demonstrated the feasibility of coupling HME with 3D printing technology, which allows for the formulation of drug delivery systems using different grades and ratios of pharmaceutical polymers.

287 citations

Journal ArticleDOI
TL;DR: In this article, the importance of thermoplastics and thermoplastic composites to additive manufacturing is discussed, and a perspective is given on the important parameters and standards needed to make AM printed objects from polymer composites more effective in cost/performance ratio.

271 citations

Journal ArticleDOI
TL;DR: In the present paper, laboratorial and industrial scale processes were reviewed, and guidelines for a rationale selection of manufacturing processes were proposed to ensure an adequate development and production according to the good manufacturing practices (GMP) (industrial scale) of amorphous solid dispersions.

254 citations

Journal ArticleDOI
TL;DR: The working principle of Hot Melt Extrusion and Fused Deposition Modelling is reviewed, and how these two technologies can be combined for the use of advanced pharmaceutical applications are reviewed.
Abstract: 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.

198 citations


Cites background from "Hot-Melt Extrusion: from Theory to ..."

  • ...A schematic diagram of a typical hot melt extruder (Reproduced with permission from reference [17], Springer, 2015)....

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  • ...A schematic diagram of a typic l t lt t er (Reproduced with permission from reference [17], Springer, 2015)....

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  • ...When the screw rotates in the extruder barrel, frictional forces are created between the rotating screw and the surface of the barrel, forming a flow channel that is responsible for transporting the mat rial fed d wn the barrel to the proximal nd of the s r w [17]....

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  • ...The extrusion process can change the physical properties of a substance when it is being forced through an orifice or die on the hot-melt extruder under controlled conditions [17]....

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  • ...Cross-section of a single and twin-screw extruder (Reproduced with permission from reference [17], Springer, 2015)....

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References
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Book
15 Dec 2000
TL;DR: Remington: The Science and Practice of Pharmacy now includes six months free online access to Facts and Comparisons's DrugfactsPlus, the leading source of drug information and pharmacist tools on the Internet.
Abstract: Remington: The Science and Practice of Pharmacy now includes six months free online access to Facts and Comparisons's DrugfactsPlus , the leading source of drug information and pharmacist tools on the Internet. Purchasers of the text will have full online access to A to Z Drug Facts , an alphabetical reference on more than 4,500 medications; Guide to Popular Natural Products , a quick reference on 125 popular medicinal herbs and natural products; Med Facts , a tool that creates patient information handouts on drugs; Drug Identifier , the most complete tool for identifying pills; and a list of over 2,000 drug manufacturers

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TL;DR: The historical background and definitions of the various systems including eutectic mixtures, solid dispersions and solid solutions, as well as the production, the different carriers and the methods used for the characterization of solid dispersion are outlined.

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01 Oct 2006
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Journal ArticleDOI
TL;DR: The amorphous state is critical in determining the solid-state physical and chemical properties of many pharmaceutical dosage forms and some of the most common methods that can be used to measure them are described.

1,864 citations

Journal ArticleDOI
TL;DR: Commercial use of solid dispersion systems during the past four decades has been very limited, primarily because of manufacturing difficulties and stability problems, but this has been changing in recent years because of the availability of surface-active and self-emulsifying carriers and the development of technologies to encapsulate solid dispersions directly into hard gelatin capsules as melts.

1,730 citations