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: As the solid dispersions with high drug load were unstable over time, demixing occurred, slightly faster for the samples prepared with the laboratory scale extruder, pointing to the predictive value of samples prepared on laboratory scale.
25 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...After this stage, the material passes through a die, which allows shape formation [11]....
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...Unlike counter-rotating extruders, they generally experience lower screw and barrel wear as they do not experience the outward ‘‘pushing’’ effect due to screw rotation [11]....
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TL;DR: An update on recent innovations reported for using hot-melt extrusion and KinetiSol Dispersing technologies to formulate poorly water-soluble APIs in amorphous solid dispersions is provided.
Abstract: Thermal processing has gained much interest in the pharmaceutical industry, particularly for the enhancement of solubility, bioavailability, and dissolution of active pharmaceutical ingredients (APIs) with poor aqueous solubility. Formulation scientists have developed various techniques which may include physical and chemical modifications to achieve solubility enhancement. One of the most commonly used methods for solubility enhancement is through the use of amorphous solid dispersions (ASDs). Examples of commercialized ASDs include Kaletra®, Kalydeco®, and Onmel®. Various technologies produce ASDs; some of the approaches, such as spray-drying, solvent evaporation, and lyophilization, involve the use of solvents, whereas thermal approaches often do not require solvents. Processes that do not require solvents are usually preferred, as some solvents may induce toxicity due to residual solvents and are often considered to be damaging to the environment. The purpose of this review is to provide an update on recent innovations reported for using hot-melt extrusion and KinetiSol® Dispersing technologies to formulate poorly water-soluble APIs in amorphous solid dispersions. We will address development challenges for poorly water-soluble APIs and how these two processes meet these challenges.
25 citations
TL;DR: A solid dispersion of APR with improved in vitro release was successfully developed using HME technology.
Abstract: Context: Solubility limitation of BCS class II drugs pose challenges to in vitro release.Objective: To investigate the miscibility of Aprepitant (APR) and Soluplus® (SOL) for hot melt extrusion (HME) viability and improved in vitro release of APR.Methods: Solubility parameters of APR and SOL from group contribution methods were evaluated. Heat–cool–heat differential scanning calorimetry (DSC) scans were assessed for determining the glass forming ability (GFA) and glass stability (GS) of APR. An optimum HME temperature was selected based on melting point depression in physical mixtures. Moisture sorption isotherms were collected using a dynamic vapor sorption (DVS) analyzer at 25 °C. A 1:4 APR:SOL physical mixture was extruded in a co-rotating 12 mm twin screw extruder and in vitro release was assessed in fasted state simulated intestinal fluid (FaSSIF) with 0.25% SLS. Extrudates were analyzed using TGA, DSC, XRD and FTIR.Results: APR was classified as a class II glass former. APR and SOL had compo...
25 citations
TL;DR: It was found the amorphous molecular dispersions prepared by spin coating had a significantly higher surface physical stability than the corresponding HME samples, which may be attributed to the increased process-related apparent drug-polymer solubility and reduced molecular mobility due to the quenching effect caused by the rapid solvent evaporation in spin coating.
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TL;DR: The Raman spectra provide real-time information about polymer-drug behavior throughout the barrel, facilitating process understanding and optimization in pharmaceutical hot-melt extrusion.
Abstract: The aim of this research was to improve understanding of material behavior in pharmaceutical hot-melt extrusion by implementing a Raman probe in each section of the barrel. Fourier-transform infrared spectroscopy measurements were performed to confirm the Raman observations. Metoprolol tartrate (MPT) concentration (10 and 40% in Eudragit RSPO), extrusion temperature (100, 120, and 140 °C), and screw speed (80 and 160 rpm) were varied to examine their influence on polymer–drug solid state throughout the barrel. When extruding a formulation with a 40% MPT concentration, the broadening of MPT peaks indicates melting of MPT between sections 2 and 3, caused by the first kneading zone. Decreasing the concentration to 10% shows an additional spectral difference (i.e., peak shifts indicating interactions between MPT and the carrier) between sections 5 and 6, due to formation of a solid solution. At a 10% MPT load, increasing the extrusion temperature does not influence the solid state or the barrel section where ...
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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