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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01 Jan 2012
TL;DR: In this article, the advantages and limitations of the hot-melt extrusion process, equipment and materials used with a focus on the applications of this technique in relevance to the pharmaceutical industry.
Abstract: The purpose of this article is to appraise the published scientific literature related to the technique of hot-melt extrusion and provide an insight en route for the operation and the process involved in this technology. This article reviews the advantages and limitations of the hot-melt extrusion process, equipment and materials used with a focus on the applications of this technique in relevance to the pharmaceutical industry. Hot-melt extrusion provides a continuous manufacturing process for moisture sensitive thermostable drugs. Extruders are of different types and twin screw extruder is the most widely used. Commonly used materials for hot-melt extrusion include polymeric carriers like ethyl cellulose, hydroxypropylcellulose, polyethylene glycol, polyethylene oxide, poly methacrylates and plasticizers like triethyl citrate, triacetin, propylene glycol, dibutyl sebacate, diethyl phthalate and glycerol monostearate. This technology offers an opportunity of earning immense intellectual property wealth as is evident from an increasing number of patents and publications using hot-melt extrusion since last few years in a variety of applications like sustained/ delayed release systems, films for transdermal or trans-mucosal drug delivery, solubility and bioavailability enhancement, taste masking and also for making amorphous materials. In near future, hot-melt extrusion would certainly emerge as an extremely preferred technology for various new chemical compounds in the pipeline.
32 citations
Cites background or methods from "Pharmaceutical Applications of Hot-..."
...Plasticizers improve the processing conditions during the manufacturing of the extruded dosage form [13] by increasing the workability and flexibility of the polymer lowering the melt viscosity, glass transition temperature (Tg) and elastic modulus of a polymeric film....
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...The materials to be used in HME process must be thermally stable in addition to acceptable physical and chemical stability [13]....
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TL;DR: It was concluded that injection molding can be applied successfully to develop sustained-release PEO/EC matrix tablets and drug release from direct compressed tablets showed faster drug release rates compared to injection-molded formulations.
Abstract: Purpose: It was the aim of the present study to develop sustained-release matrix tablets by means of injection molding of ethylcellulose (EC) and polyethylene oxide (PEO) mixtures and to evaluate the influence of process temperature, matrix composition, and viscosity grade of EC and PEO on processability and drug release. Methods: Formulations consisting of metoprolol tartrate (MPT, concentration: 30%), EC plasticized by dibutyl sebacate, and PEO were extruded and consequently injection molded into tablets. The influence of process temperature (120°C and 140°C), matrix composition, viscosity grade of EC (4, 10, 20, 45, and 100 mPa·s) and PEO (7 × 106, 1 × 106, and 1 × 105 Mw) on processability and drug release was determined. Results: Formulations consisting of 70% EC and 30% MPT showed incomplete drug release, whereas drug release was too fast for formulations without EC. Higher PEO concentrations increased drug release. Formulations containing 30% metoprolol, EC, and different concentrations of PEO show...
32 citations
TL;DR: Specific applications of amorphous solid dispersion in the formulation of herbal drugs or bioactive natural products are reviewed to reflect the growing interest in this relatively neglected area.
Abstract: Solid state manipulation by amorphous solid dispersion has been the subject of intensive research for decades due to their excellent potential for dissolution and bioavailability enhancement. The present review aims to highlight the latest advancement in this area, with focus on the fundamentals, characterization, formulation development and manufacturing of amorphous solid dispersions as well as the new generation amorphization technologies. Additionally, specific applications of amorphous solid dispersion in the formulation of herbal drugs or bioactive natural products are reviewed to reflect the growing interest in this relatively neglected area.
31 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...Screw extruders use a single or double screw system to heat, intimately mix and convey a drug, polymer and possibly a plasticizer above their glass transition temperatures or melting points out of a die [80,81]....
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11 Oct 2013
TL;DR: This chapter describes the development and use of process analytical technology tools for a continuous HME process, monitored with generic sensors and a near-infrared (NIR) spectrometer in real time, using SIPAT (Siemens platform to collect, display and extract process information) and additional components developed as needed.
Abstract: The implementation of continuous manufacturing in the pharmaceutical industry has been of increasing interest over the last years. This chapter focuses on continuous hot melt extrusion (HME) processing as well as on the continuous downstream options that are available. Furthermore, process analytical technology (PAT) tools and the integration of such tools in process control environment are presented. In general, real-time pharmaceutical process verification is accomplished by monitoring univariate (temperature, pressure, etc.) and multivariate (spectra, images, etc.) process parameters and quality attributes, to provide an accurate state estimation of the process, required for advanced control strategies. This chapter describes the development and use of such tools for a continuous HME process, monitored with generic sensors and a near-infrared (NIR) spectrometer in real time, using SIPAT (Siemens platform to collect, display and extract process information) and additional components developed as needed.
31 citations
TL;DR: The current review portray the historical milestones, classification, probable mechanisms for enhancement of solubility, manufacturing processes at commercial level along with pioneer breakthroughs in field that enunciates the versatile pharmaceutical application for categories including anti-cancer and anti-retroviral drugs.
Abstract: The solubility of drugs is one of the most challenging aspects in developing formulations for novel drug discovery. Myriad of approaches have been developed and tested to overcome the associated intricacies involved with poor water soluble drugs. Out of the available technologies, solid dispersion (SD) method that significantly enhances the solubility and bioavailability by reducing particle size to a micro-molecular level is often viewed as a promising strategy. Although conceptual basis of manufacturing processes involved in SD method have been reported, formulation characteristics addressing solubility issues remains yet elusive. The current review portray the historical milestones, classification, probable mechanisms for enhancement of solubility, manufacturing processes at commercial level along with pioneer breakthroughs in field that enunciates the versatile pharmaceutical application for categories including anti-cancer and anti-retroviral drugs. Besides, our article also highlights the translational implications of drug development by SD method hitherto unreported.
31 citations
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