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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TL;DR: The results showed that the drug was not completely released after 24 h for tablets developed by the wet granulation process using all three lipids, indicating the suitability of the process for formulating sustained release tablets.
32 citations
TL;DR: Investigation of downstream processing of nanofibrous amorphous solid dispersions to generate tablet formulation and the influence of excipients on dissolution properties and the feasibility of scaled-up rotary press tableting confirmed that ITR was chemically stable both in the course of downstreamprocessing and storage.
32 citations
Cites methods from "Pharmaceutical Applications of Hot-..."
...Polarized light microscopy image of filtered sample after dissolution of tablet with (a) SSF and (b) Raman spectra of (1) SSF, (2) crystalline ITR, and (3) filtered powder....
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...Polarized light microscopy image of filtered sample after dissolution of tablet with (a) MgSt and (b) Raman spectra of (1) MgSt, (2) crystalline ITR, and (3) crystal in the...
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TL;DR: In this article, the authors provide a panorama for the recent progress of fused deposition modeling (FDM) technology in the manufacturing of discontinuous fiber reinforced thermoplastic composites and identify the main challenges and outlook for the future development of this 3D printing technology in fiber reinforced composites.
Abstract: Fused deposition modeling (FDM) is one of the most widely utilized additive manufacturing techniques by virtue of its numerous merits, such as easy operation, low cost, low energy consumption and little-to-no waste. Based on its simple configuration and extrusion-assisted process, the research and development of this technique is gradually shifting from traditional prototype printing to high-performance composite fabrication. This review provides a panorama for the recent progress of FDM technology in the manufacturing of discontinuous fiber reinforced thermoplastic composites. The entire production chain from the very beginning of FDM filament preparation to the latest stage in large-scale manufacturing process is discussed. The enlightening strategy in multi-axis FDM field is highlighted as it possesses a great potential to manufacture the next-generation composites with superior geometric complexity and flexible fiber alignment. This review also identifies the main challenges and outlook for the future development of this 3D printing technology in fiber reinforced composites.
32 citations
TL;DR: Investigation of the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate and ketoconazole solid dispersions showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphously despite 5% moisture uptake.
Abstract: Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials® to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardle...
32 citations
TL;DR: In this article, the authors explored the application of melt granulation technology to develop a high drug loaded sustained release matrix tablet of Metformin HCl using hydroxypropylcellulose (HPC) as a hydrophilic binder and stearic acid as an extrusion aid for producing cohesive granules.
32 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...[23] Crowley MM, Zhang F, Repka MA, et al....
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...However, there is no conversion of crystalline drug substance to amorphous form [22,23]....
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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