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 , the authors evaluated the influence of adjuvants and drug loading on the development of amorphous solid dispersion of flubendazole-copovidone by hot-melt extrusion.
5 citations
01 Jan 2012
TL;DR: The purpose of this chapter is to describe emerging technologies for solubility enhancement, allowing the reader to gain an understanding of their utility.
Abstract: The need for novel processes and formulation-based techniques to enhance the solubility of poorly water-soluble drugs has increased substantially in recent years. This is primarily due to the limitations of traditional techniques such as physical and chemical stability of the drug substance or the need for toxic solvents that some techniques require. Alternative solubility-enhancement techniques have emerged in recent years to mitigate issues such as these. The purpose of this chapter is to describe emerging technologies for solubility enhancement, allowing the reader to gain an understanding of their utility.
5 citations
01 Jan 2018
TL;DR: This chapter is a general introduction to Amorphous APIs and most commonly discussed production and characterization methods.
Abstract: Producing Amorphous Active Pharmaceutical Ingredients offers an enhanced drug release that is caused by the increase in its dissolution rate This improvement enables higher bioavailability and bioactivity of such solid APIs Possibilities to control the drug release and its bioactivity offer new opportunities to design more effective and stable medications This chapter is a general introduction to Amorphous APIs and most commonly discussed production and characterization methods
5 citations
TL;DR: In this paper , the authors present a systematic study of the milling and tableting of an extruded amorphous solid dispersions (ASDs) with hypromellose acetate succinate (HPMCAS) as a carrier polymer.
Abstract: The downstream processing of hot-melt extruded amorphous solid dispersions (ASDs) into tablets is challenging due to the low tabletability of milled ASDs. Typically, the extrudate strand is sized before milling, as the strand cannot be fed directly into the milling system. At the lab scale, the strand can be sized by hand-cutting before milling. For scaling up, pelletizers or chill roll and flaker systems can be used to break strands. Due to the different techniques used, differences in milling and tablet compaction are to be expected. We present a systematic study of the milling and tableting of an extruded ASD of itraconazole with hypromellose acetate succinate (HPMCAS) as a carrier polymer. The strand was sized using different techniques at the end of the extruder barrel (hand-cutting, pelletizer, or chill roll and flaker) before being milled at varying milling speeds with varying screen sizes. The effects of these variables (sizing technology, milling speed, and screen size) on the critical quality attributes (CQAs) of the milled ASD, such as yield, mean particle size (D50), tablet compaction characteristics, and tablet dissolution, were established using response surface methodology. It was found that the CQAs varied according to sizing technology, with chill roll flakes showing the highest percentage yield, the lowest D50, and the highest tabletability and dissolution rate for itraconazole. Pearson correlation coefficient tests indicated D50 as the most important CQA related to tabletability and dissolution. For certain milling conditions, the milling of hand-cut filaments results in similar particle size distributions (PSDs) to the milling of pellets or chill roll flakes.
5 citations
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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