Pharmaceutical Applications of Hot-Melt Extrusion: Part I
TL;DR: The pharmaceutical applications of hot-melt extrusion, including equipment, principles of operation, and process technology, are reviewed and the physicochemical properties of the resultant dosage forms are described.
Abstract: Interest in hot-melt extrusion techniques for pharmaceutical applications is growing rapidly with well over 100 papers published in the pharmaceutical scientific literature in the last 12 years. Hot-melt extrusion (HME) has been a widely applied technique in the plastics industry and has been demonstrated recently to be a viable method to prepare several types of dosage forms and drug delivery systems. Hot-melt extruded dosage forms are complex mixtures of active medicaments, functional excipients, and processing aids. HME also offers several advantages over traditional pharmaceutical processing techniques including the absence of solvents, few processing steps, continuous operation, and the possibility of the formation of solid dispersions and improved bioavailability. This article, Part I, reviews the pharmaceutical applications of hot-melt extrusion, including equipment, principles of operation, and process technology. The raw materials processed using this technique are also detailed and the physicochemical properties of the resultant dosage forms are described. Part II of this review will focus on various applications of HME in drug delivery such as granules, pellets, immediate and modified release tablets, transmucosal and transdermal systems, and implants.
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Dissertation•
28 Feb 2018
TL;DR: In this paper, indomethacin-loaded self-nano-emulsifying drug delivery systems (SNEDDS) were developed in liquid, solid and carrier-mediated formulations in order to improve the solubility of this model poorly water soluble drug.
Abstract: In this study, indomethacin-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were developed in liquid, solid and carrier-mediated formulations in order to improve the solubility of this model poorly water soluble drug. Liquid SNEDDS based on Capryol™ 90 (oil phase), Cremophor® RH 40 (surfactant) and Transcutol® HP (co-surfactant) were thermodynamically stable and produced clear nanoemulsions upon dilution. Optimized liquid formulations were transformed into solid SNEDDS by adsorption onto the inert carriers Syloid® XDP 3150, Neusilin® US2 and Florite® PS-200. Ratios of adsorbent: liquid SNEDDS of 1:1.5 and 1:2 resulted in solid SNEDDS formulations that exhibited fair to passable powder flow properties. Carrier-based solid SNEDDS formulations were developed using the solid self-emulsifying carriers Gelucire® 44/14 and Gelucire® 48/16 and prepared by hot melt extrusion. The absorbent-based solid SNEDDS maintained the self-nanoemulsification properties of the original liquid SNEDDS formulations, with solid state analysis suggesting that the drug had remained in a dissolved state within these formulations. Similarly, physical characterization of the carrier-based solid SNEDDS formulations indicated that the drug was molecularly dispersed within the system and that the self-nanoemulsifying properties of the carrier were unchanged. The only exception was those formulations prepared at the highest drug: carrier ratio (3: 10). For both absorbent-based and carrier-based solid SNEDDS, the in vitro dissolution efficiency was significantly higher than that obtained for the pure drug. However, incorporation of adsorbents into Gelucire®-based solid SNEDDS formulations resulted in reduced dissolution of the drug. Gelucire®48/16-based solid SNEDDS prepared at 50oC were more physically stable to storage at 30oC/75% RH for 6 months than formulations processed at 40oC, suggesting that complete melting of the carrier during manufacture is essential for production of physically stable formulations. Overall, a range of liquid, solid and carrier-based SNEDDS formulations were successfully developed and offer useful alternatives to improving the solubility of poorly water-soluble drugs.
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Cites background or methods from "Pharmaceutical Applications of Hot-..."
...In addition, pharmaceutical materials that can be used in HME should be pure and safe, similarly to the materials used for traditional manufacturing methods (Crowley et al., 2007)....
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...Low molecular weight polyethylene glycol and surfactants are examples of the materials that can be used as plasticizers during manufacturing by HME (Crowley et al., 2007)....
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TL;DR: In this article, three extrusion techniques, wet extrusion, solid lipid extrusion and melt extrusion are introduced and their potential and limits with respect to dissolution profiles are described, depending on the selected matrix material and the process parameters all types of dissolution profiles can be achieved.
Abstract: Beim Design pharmazeutischer Produkte ist die Freisetzung nicht allein wichtig, aber von besonderer Bedeutung. Je nach Eigenschaften der zu verarbeitenden Wirkstoffe und Therapieziel beinhaltet die gezielte Freisetzung unterschiedliche Aufgabenstellungen. Es werden drei Techniken der pharmazeutischen Extrusion, die Feuchtextrusion, die Festfettextrusion und die Schmelzextrusion, vorgestellt und deren Moglichkeiten und Grenzen zur Beeinflussung der Freisetzung beschrieben. Das groste Potenzial zum Freisetzungsdesign bietet die Schmelzextrusion. Je nach Auswahl der Matrixbildner und der Verarbeitung lassen sich alle Aufgabenstellungen hinsichtlich der Freisetzung losen.
Dissolution is not the only but a major issue in the design of pharmaceutical products. The technological tasks differ depending on the properties of the active pharmaceutical ingredient and the therapeutic goal. Three extrusion techniques, wet extrusion, solid lipid extrusion and melt extrusion, are introduced and their potential and limits with respect to dissolution profiles are described. The most flexible design of dissolution profiles can be achieved by melt extrusion. Depending on the selected matrix material and the process parameters all types of dissolution profiles can be achieved.
8 citations
Journal Article•
TL;DR: In this paper, the effect of extrusion and plasticiser on the thermal and melt viscosity properties of the blends was coincidentally monitored, and a vital advantage of this study is the ability to fine tune the properties of matrix by varying material concentrations, making these promising candidates for tissue engineering applications.
Abstract: In the past two decades, the repair and reconstruction of musculoskeletal tissues using biodegradable scaffold materials has emerged as one of the most promising approaches in tissue engineering. The aim of this study is to process, via hot melt extrusion, the biodegradable and biocompatible polymeric materials; poly(ethylene oxide) (PEO), poly(ethylene glycol) (PEG), ⍺lactose monohydrate and poly(e-caprolactone) (PCL), and investigate their suitability in tissue regenerating applications. Concentrations of the polymer blends were varied in order to optimise the degradation rate of the matrix blend. The effect of extrusion and plasticiser on the thermal and melt viscosity properties of the blends was coincidentally monitored. Materials of both pellet and powder compositions were compared in order to determine which composition provided optimum results. Blends were characterised using melt flow index (MFI), differential scanning calorimetry (DSC), rheometry and degradation analysis. Addition of plasticiser was found to cause a decrease in viscosity and melt temperature of the materials, so too was the extrusion process albeit to a lesser extent, while addition of filler increased melt viscosity and melt temperature of the blend. A vital advantage of this study is the ability to fine tune the properties of the matrix by varying material concentrations, making these promising candidates for tissue engineering applications.
8 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...PEG is a low molecular weight plasticiser; allowing it to increase the free volume between polymer chains and in turn enhance mobility (Crowley et al. 2007)....
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TL;DR: The use of microstructural and dispersion analysis appeared to be complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.
Abstract: Multifractal geometry has become a powerful tool to describe complex structures in many fields. Our first aim was to combine imaging and multifractal analysis to better understand the microstructure of pharmaceutical extrudates. A second objective was to study erosion/dispersion behavior of the formulations because it would condition release of any drug. Different formulations containing a lipid, a polymer and different silica based inorganic carriers were produced by hot-melt extrusion at various screw speeds. Multifractal analysis was based on scanning electron microscopy/energy dispersive X-Ray spectroscopy images. This microstructural analysis was complemented with dynamic optical imaging of formulation erosion/dispersion behavior. Multifractal analysis indicated that inorganic carrier type and concentration as well as the screw speed affected the microstructure of the extrudates. The aqueous erosion/dispersion study showed that only the type and concentration of inorganic carrier were important. The use of microstructural and dispersion analysis appeared to be complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.
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References
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1,883 citations
Book•
01 Jan 1995
TL;DR: The authors provided the basic building blocks of polymer science and engineering by coverage of fundamental polymer chemistry and materials topics given in Chapters 1 through 7 and provided information on the exciting new materialsnow available and the emerging areas of technological growth that could motivate a new generation of scientists and engineers.
Abstract: From the Book:
PREFACE: At least dozens of good introductory textbooks on polymer science and engineering are now available. Why then has yet another book been written?
The decision was based on my belief that none of the available texts fully addresses the needs of students in chemical engineering. It is not that chemical engineers are a rare breed, but rather that they have special training in areas of thermodynamics and transport phenomena that is seldom challenged by texts designed primarily for students of chemistry or materials science. This has been a frustration of mine and of many of my students for the past 15 years during which I have taught an introductory course, Polymer Technology, to some 350 chemical engineering seniors. In response to this perceived need, I had written nine review articles that appeared in the SPE publication Plastics Engineering from 1982 to 1984. These served as hard copy for my students to supplement their classroom notes but fell short of a complete solution.
In writing this text, it was my objective to first provide the basic building blocks of polymer science and engineering by coverage of fundamental polymer chemistry and materials topics given in Chapters 1 through 7.
As a supplement to the traditional coverage of polymer thermodynamics, extensive discussion of phase equilibria, equation-of- state theories, and UNIFAC has been included in Chapter 3. Coverage of rheology, including the use of constitutive equations and the modeling of simple flow geometries, and the fundamentals of polymer processing operations are given in Chapter 11.
Finally, I wanted to provide information on the exciting new materialsnowavailable and the emerging areas of technological growth that could motivate a new generation of scientists and engineers. For this reason, engineering and specialty polymers are surveyed in Chapter 10 and important new applications for polymers in separations (membrane separations), electronics (conducting polymers), biotechnology (controlled drug release), and other specialized areas of engineering are given in Chapter 12. In all, this has been an ambitious undertaking and I hope that I have succeeded in at least some of these goals.
Although the intended audience for this text is advanced undergraduates and graduate students in chemical engineering, the coverage of polymer science fundamentals (Chapters 1 through 7) should be suitable for a semester course in a materials science or chemistry curriculum.
Chapters 8 through 10 intended as survey chapters of the principal categories of polymers commodity thermoplastics and fibers, network polymers (elastomers and thermosets), and engineering and specialty polymers may be included to supplement and reinforce the material presented in the chapters on fundamentals and should serve as a useful reference source for the practicing scientist or engineer in the plastics industry.
981 citations
TL;DR: A comparison of the carbonyl stretching region of γ indomethacin, known to form carboxylic acid dimers, with that of amorphous indometHacin indicated that the amorphously phase exists predominantly as dimers.
Abstract: Purpose. To study the molecular structure of indomethacin-PVP amorphous solid dispersions and identify any specific interactions between the components using vibrational spectroscopy.
904 citations
Book•
01 Jan 1988
TL;DR: In this article, the elastic properties of polymeric solids and their properties of rubber are discussed. But they focus on the structure of the molecule rather than the properties of the solids.
Abstract: Introduction. 1: Structure of the molecule. 2: Structure of polymeric solids. 3: The elastic properties of rubber. 4: Viscoelasticity. 5: Yield and fracture. 6: Reinforced polymers. 7: Forming. 8: Design. Further reading, Answers, Index
790 citations
TL;DR: Improved bioavailability was achieved again demonstrating the value of the technology as a drug delivery tool, with particular advantages over solvent processes like co-precipitation.
790 citations