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 article, aripiprazole (ARIP) is used as a poor water-soluble model drug for solid dispersions and its dissolution characteristics are tested for different drug contents and various PVP-to-poloxamer ratios.
Abstract: Poly(vinyl pyrrolidone) (PVP)/poloxamer-188 blends were used as appropriate carriers for the preparation of solid dispersions by hot melt extrusion using aripiprazole (ARIP) as a poor water-soluble model drug. The physical state of ARIP in solid dispersions and its dissolution characteristics were tested for different drug contents and various PVP-to-poloxamer ratios. From TG analysis it was found that all materials were stable at the tested extrusion temperature conditions (110–120 °C) while amorphous drug dispersions were prepared in all cases, due to the miscibility of the polymer matrix with ARIP drug. Furthermore, hydrogen bonds were identified between ARIP (>N–H) and PVP (>C=O) using FT-IR analysis. Finally, ARIP dissolution rate from SDs was pH dependant and increased as the drug content decreased.
36 citations
Cites background or methods from "Pharmaceutical Applications of Hot-..."
...Hot-melt extrusion (HME) has increasingly been reported in the pharmaceutical literature as an appropriate technique for preparing pharmaceutical solid dispersions [1–3]....
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...As a large number of newly developed chemical entities are poorly soluble in water, it is understandable that much research effort has been devoted to utilizing the HME process to prepare drugs with enhanced bioavailability [2, 3]....
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TL;DR: It is found that both mechanical and thermal energy inputs affect the conversion of crystalline NIF into an amorphous form, and they also affect the level of mixing and the degree of homogeneity in NIF ASDs.
36 citations
TL;DR: Careful choice of manufacturing process can be used to tune material properties of ASDs to make them more amenable for downstream operations like tableting.
36 citations
01 Jan 2014
TL;DR: The role of excipients in the stabilization of amorphous solid dispersions by influencing physicochemical properties of the drug molecule of interest is discussed in this paper, and the classification of various excipient is categorized in detail, covering polymers, solubilizers, plasticizers, antioxidants and other suitable fillers.
Abstract: Pharmaceutical excipients play a significant role in stabilization of amorphous solid dispersions, as these systems are thermodynamically unstable This chapter illustrates the challenges associated with amorphous solid dispersion stability and the role that excipients play in stabilization of amorphous solid dispersions by influencing the physicochemical properties of the drug molecule of interest The classification of various excipients is categorized in detail, covering polymers, solubilizers, plasticizers, antioxidants, and other suitable fillers The impact of excipients on various amorphous solid dispersion technologies is also discussed in detail Discovery of newer polymers and greater understanding of excipients’ role in the stabilization of amorphous solid dispersion are the primary reasons for successful launch of several marketed drug products In addition, safety and regulatory aspects of these excipients also need to be considered for the development of successful products In summary, excipients play a significant role in stabilizing amorphous solid dispersions, maximizing bioavailability, and overcoming absorption issues associated with poorly soluble drugs
35 citations
TL;DR: Under non‐supersaturating conditions in the dissolution medium, drug nanocrystals in the HPC‐based nanocomposites dissolved faster than the amorphous drug in Soluplus®‐based ASD.
35 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...On the other hand, pharmaceutical hot-melt extrusion (HME), which allows for intimate molecular interactions between a drug in a molten polymer and formation of an ASD [45,46], has found common use as the most popular solvent-less fusion-based method....
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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