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Journal ArticleDOI

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.
Citations
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Journal ArticleDOI
TL;DR: The obtained rheological results are relevant for understanding and predicting HME processability and downstream processing such as injection moulding (e.g., barrel temperature selection and mold temperature selection).
Abstract: The aim of this study was to investigate (i) the influence of drug solid-state (crystalline or dissolved in the polymer matrix) on the melt viscosity and (ii) the influence of the drug concentration, temperature and shear rate on polymer crystallization using rheological tests Poly (ethylene oxide) (PEO) (100000 g/mol) and physical mixtures (PM) containing 10–20–30–40% (w/w) ketoprofen or 10% (w/w) theophylline in PEO were rheologically characterized Rheological tests were performed (frequency and temperature sweeps in oscillatory shear as well as shear-induced crystallization experiments) to obtain a thorough understanding of the flow behaviour and crystallization of PEO-drug dispersions Theophylline did not dissolve in PEO as the complex viscosity (η*) of the drug-polymer mixture increased as compared to that of neat PEO In contrast, ketoprofen dissolved in PEO and acted as a plasticizer, decreasing η* Acting as a nucleating agent, theophylline induced the crystallization of PEO upon cooling from the melt On the other hand, ketoprofen inhibited crystallization upon cooling Moreover, higher concentrations of ketoprofen in the drug-polymer mixture increasingly inhibited polymer crystallization However, shear-induced crystallization was observed for all tested mixtures containing ketoprofen The obtained rheological results are relevant for understanding and predicting HME processability (eg, barrel temperature selection) and downstream processing such as injection moulding (eg, mold temperature selection)

23 citations


Cites background from "Pharmaceutical Applications of Hot-..."

  • ...In the pharmaceutical industry, hot-melt extrusion (HME) is a continuous and highly flexible manufacturing technology used for the production of solid dispersions (SDs) (1)....

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Journal ArticleDOI
TL;DR: In this article, an inner rotating knife is proposed for stabilizing melt flow in a hot melt extrusion (HME) process. But due to heat dissipation in the small gap between rotor and stator, this device has to be fitted with a separate low-speed drive and cannot be coupled directly to the main extruder shaft.

22 citations


Cites background from "Pharmaceutical Applications of Hot-..."

  • ...Starting from the polymer and plastic industry, hot-melt extrusion (HME) has also found numerous applications in pharmaceutical manufacturing practice (Breitenbach, 2002; Crowley et al., 2004, 2007; Repka et al., 2007)....

    [...]

Journal ArticleDOI
TL;DR: The study has shown that it is possible to use a single NIR spectroscopy technique to monitor opaque and transparent melts during HME, and to simultaneously monitor two distinct components within a formulation.

22 citations

Book ChapterDOI
01 Jan 2013
TL;DR: This chapter appraises the role of melt extrusion as a solubilization and bioavailability enhancement technique and displays the journey and evolution of this important processing technology into an established pharmaceutical manufacturing platform.
Abstract: This chapter appraises the role of melt extrusion as a solubilization and bioavailability enhancement technique. The introductory chapter highlights major aspects of hot melt extrusion (HME) technology as applied in the pharmaceutical industry, particularly processing techniques, material considerations, recent innovative applications of melt extrusion in drug delivery system design, and a review of current HME-based formulations (marketed or under commercial development). The chapter also focuses on key development aspects of HME processes, such as material sparing screening approaches, process formulation relationships, and stability evaluation of prototype formulations, which emphasize the clinical and biological significance of this technique. In addition, it displays the journey and evolution of this important processing technology into an established pharmaceutical manufacturing platform. The chapter describes several case studies wherein melt extrusion has been utilized to develop commercial drug products.

22 citations

Journal ArticleDOI
TL;DR: Dissolution in 250 mL ofFasted state simulated gastric fluid revealed that single tablet of Imodium® and SJU1 showed >85% of release within 15 minutes, thus demonstrating its ability to deter multi-dose oral abuse.

22 citations

References
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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

Journal ArticleDOI
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

Journal ArticleDOI
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