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: In this paper, a mathematical model consisting of mass and energy balance partial differential equations is developed and parameters related to material transportation are inferred from experimental data collected from a pilot plant, which is relative to the output residence time distribution of active product.
6 citations
TL;DR: It is demonstrated that in the pharmaceutically relevant HME processing temperature range these polymers behave similarly to yield-stress fluids and flow only when the applied stress exceeds a critical stress value.
6 citations
TL;DR: By using glycerol and hot-melt extrusion, the potential issues of conventional methods were successfully addressed and the formulation displayed the desired physical and chemical stability in texture profile analysis and in the in vitro drug release studies.
Abstract: Patients who suffer from dysphagia have difficulty in swallowing hard tablets and capsules; hence, gelatin-based soft-chew dosages are used as an alternative and novel drug delivery approach to overcome this problem. However, the conventional method of producing gelatin-based soft-chew dosages has many potential issues. The objective of this study was to use glycerol and the hot-melt extrusion technique to address potential issues and optimize the formulation. Gelatin, acetaminophen, saccharin, xylitol, and sodium chloride and six different ratios of water and glycerol were used in the seven formulations. Extrusion process temperature of formulations 1–6 and formulation 7 were 90°C and 140°C, respectively. Near-infrared spectra were collected during extrusion to monitor quality consistency. Scanning electron microscopic images of the cross-section of the soft-chew dosages were recorded. Differential scanning calorimetry (DSC) was used to characterize the crystal states of each formulation. Texture profile analysis was used to evaluate the physical properties of the tablets. In vitro drug release characteristics were studied. A 45-day stability study was carried out to evaluate the stability of each formulation. Near-infrared spectra showed that formulations 1–6 were uniform while formulation 7 was not. From the DSC results, formulations 1 and 2 showed crystallinity of acetaminophen. Formulation 5 displayed the desired physical and chemical stability in texture profile analysis and in the in vitro drug release studies. By using glycerol and hot-melt extrusion, the potential issues of conventional methods were successfully addressed.
6 citations
Cites background or methods from "Pharmaceutical Applications of Hot-..."
...(2) Soft chews produced by HME demonstrate good content uniformity and uniform dispersion of fine particles, ensuring uniformity and stability at different pH and moisture levels (17,18)....
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...(3) Moreover, in-line processing analytical technology (PAT) tools can be easily implemented, and real-time monitoring is possible (18)....
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...3) Moreover, inline processing analytical technology (PAT) tool can be easily implemented, and real-time monitoring becomes a possibility (Crowley et al. 2007) In view of so many advantages of using HME to produce soft-chews, however, based on the research we have done, there has no report showed…...
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...(Crowley et al. 2007; Douroumis 2012)....
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TL;DR: The buccal cavity can be most useful for delivery of drugs for systemic effects, which may include rapid onset of action, avoidance of presystemic elimination, and transformation by intestinal mucosal enzymes.
Abstract: The buccal cavity can be most useful for delivery of drugs for systemic effects. Advantages can include rapid onset of action, avoidance of presystemic elimination, which may include gastrointestinal degradation, first-pass clearance by the liver, or transformation by intestinal mucosal enzymes, e.g., CYP450. Exposure of a bioactive to gastric acid is also avoided. Rate of delivery can also be controlled by formulation approaches. Drugs must be carefully selected for delivery via the buccal route. For example the dose must be low and the physicochemical properties must be appropriate. Dose must be low and the physicochemical properties must be appropriate. Furthermore, as different regions of the cavity possess differing permeation characteristics, it may be necessary to ensure prolonged contact between the delivery system and the optimal region for consistent and reliable absorption. Such possibilities, together with manufacturing processes for buccal delivery systems, are presented and discussed in this chapter.
6 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...Such interest is reflected by over 200 research papers and several reviews on the topic [119–123]....
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03 Jul 2014
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Cites background from "Pharmaceutical Applications of Hot-..."
...This results in comparatively high shear forces [200, 203, 210]....
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...Third, the melting capacity is limited, which causes poor temperature uniformity in the extrudates [200]....
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...At the same time, such systems may suffer from air entrapment, the generation of high pressures, and low maximum screw speeds and output [200]....
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...Especially screw extruders are used for the manufacturing of granules or pellets that are further processed into capsules or tablets [200, 203-205]....
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...Currently, more than half of all plastic products including bags, sheets, and pipes are manufactured by this process [200]....
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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