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: A small molecule drug, indomethacin, was utilized as a model compound and a parameter "Toughness" calculated by stiffness test was identified to quantitatively describe the printability of filaments in the FDM 3D printer.
45 citations
TL;DR: In order to reduce the number of unit operations required to produce a final pharmaceutical product, spray drying showed higher feasibility over HME to produce cocrystals within a carrier excipient.
45 citations
TL;DR: Low-viscosity HPC-SL and -SSL can be employed to produce chemically stable SDs of poorly as well as highly water-soluble drugs using various pharmaceutical processes in order to control drug dissolution.
Abstract: Hydroxypropylcellulose (HPC)-SL and -SSL, low-viscosity hydroxypropylcellulose polymers, are versatile pharmaceutical excipients. The utility of HPC polymers was assessed for both dissolution enhancement and sustained release of pharmaceutical drugs using various processing techniques. The BCS class II drugs carbamazepine (CBZ), hydrochlorthiazide, and phenytoin (PHT) were hot melt mixed (HMM) with various polymers. PHT formulations produced by solvent evaporation (SE) and ball milling (BM) were prepared using HPC-SSL. HMM formulations of BCS class I chlorpheniramine maleate (CPM) were prepared using HPC-SL and -SSL. These solid dispersions (SDs) manufactured using different processes were evaluated for amorphous transformation and dissolution characteristics. Drug degradation because of HMM processing was also assessed. Amorphous conversion using HMM could be achieved only for relatively low-melting CBZ and CPM. SE and BM did not produce amorphous SDs of PHT using HPC-SSL. Chemical stability of all the drugs was maintained using HPC during the HMM process. Dissolution enhancement was observed in HPC-based HMMs and compared well to other polymers. The dissolution enhancement of PHT was in the order of SE > BM > HMM > physical mixtures, as compared to the pure drug, perhaps due to more intimate mixing that occurred during SE and BM than in HMM. Dissolution of CPM could be significantly sustained in simulated gastric and intestinal fluids using HPC polymers. These studies revealed that low-viscosity HPC-SL and -SSL can be employed to produce chemically stable SDs of poorly as well as highly water-soluble drugs using various pharmaceutical processes in order to control drug dissolution.
44 citations
TL;DR: This review article focuses on advances in HME technology, which include improvement in the weaknesses of HME, patient-centric formulations, and the outlook for uses such as formulation development.
Abstract: Hot Melt Extrusion (HME) technology is a widely used for manufacturing process in the plastic and pharmaceutical industries and is an efficient and simple for the production of a solid dispersion. This technique is an environmental friendly, continuous process that does not use solvents. It is time and cost efficient and can be easily scaled up. In addition, HME may be used in conjunction with other technologies to effectively increase the solubility and dissolution rate of poorly water-soluble drugs. Numerous research papers on the progress of HME technology in the pharmaceutical industry have been written, and products manufactured using HME have been approved by the FDA. However, there are some drawbacks to the products manufactured using through HME. These are related to the high energy input coming from the applied shear forces and high temperature, which could lead to drug or polymer degradation and thus significantly impact the product quality. Despite these disadvantages, HME has been employed in various advanced applications, such as taste masking and targeted drug delivery. This review article focuses on advances in HME technology, which include improvement in the weaknesses of HME, patient-centric formulations, and the outlook for uses such as formulation development.
44 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...The use of plasticizers affects the physico-mechanical properties and drug release behavior of the hot-melt extrudates; plasticizers increase the elasticity and flexibility of the extrudates (Crowley et al. 2007)....
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...Thus, the drug choice is limited by the requirement of thermal stability at process temperature (Crowley et al. 2007)....
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TL;DR: Ethyl cellulose formulations containing zidovudine and lamivudine, with 5-10% by weight of TEC as the plasticizer are suitable for processing by hot melt extrusion, while PEG-6000 recrystallized upon cooling makes it unsuitable for use in the proposed controlled release formulations.
44 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