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.
Citations
More filters
TL;DR: The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release fromhydrophobic-lipids matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.
49 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...HME is a continuous, simple, easy to scale up and efficient process (Maniruzzaman et al., 2012; Patil et al., 2014; Repka et al., 2007)....
[...]
TL;DR: The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion and downstream processing parameters on the water uptake properties of amorphous solid dispersions.
Abstract: Objective
The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion and downstream processing parameters on the water uptake properties of amorphous solid dispersions.
Methods
Three polymers and a model drug were used to prepare amorphous solid dispersions utilizing the hot melt extrusion technology. The sorption–desorption isotherms of solid dispersions and their physical mixtures were measured by the dynamic vapour sorption system, and the effects of polymer hydrophobicity, hygroscopicity, molecular weight and the hot melt extrusion process were investigated. Fourier transform infrared (FTIR) imaging was performed to understand the phase separation driven by the moisture.
Key findings
Solid dispersions with polymeric carriers with lower hydrophilicity, hygroscopicity and higher molecular weight could sorb less moisture under the high relative humidity (RH) conditions. The water uptake ability of polymer–drug solid dispersion systems were decreased compared with the physical mixture after hot melt extrusion, which might be due to the decreased surface area and porosity. The FTIR imaging indicated that the homogeneity of the drug molecularly dispersed within the polymer matrix was changed after exposure to high RH.
Conclusion
Understanding the effect of formulation and processing on the moisture sorption properties of solid dispersions is essential for the development of drug products with desired physical and chemical stability.
48 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...More than 40% of newly discovered active pharmaceutical ingredients (API)([1]) possess unfavourable physical properties,([2]) and most of them belong to the biopharmaceutics classification system class II or IV, characterized by poor aqueous solubility and oral bioavailability....
[...]
Dissertation•
19 Oct 2015
48 citations
TL;DR: The extrusion process space, which should be selected to ensure that the drug is solubilized in the polymer with minimal thermal exposure, is critical in ensuring the performance, stability and purity of the solid dispersion.
Abstract: Objective
The use of corotating twin screw hot-melt extruders to prepare amorphous drug/polymer systems has become commonplace. As small molecule drug candidates exiting discovery pipelines trend towards higher MW and become more structurally complicated, the acceptable operating space shifts below the drug melting point. The objective of this research is to investigate the extrusion process space, which should be selected to ensure that the drug is solubilized in the polymer with minimal thermal exposure, is critical in ensuring the performance, stability and purity of the solid dispersion.
Methods
The properties of a model solid dispersion were investigated using both corotating and counter-rotating hot-melt twin-screw extruders operated at various temperatures and screw speeds. The solid state and dissolution performance of the resulting solid dispersions was investigated and evaluated in context of thermodynamic predictions from Flory–Huggins Theory. In addition, the residence time distributions were measured using a tracer, modelled and characterized.
Key findings
The amorphous content in the resulting solid dispersions was dependent on the combination of screw speed, temperature and operating mode.
Conclusions
The counter-rotating extruder was observed to form amorphous solid dispersions at a slightly lower temperature and with a narrower residence time distribution, which also exhibited a more desirable shape.
48 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...On the other hand, corotating extruders are perceived to offer a wider range of mixing capabilities.([6]) However, there is a great deal of overlap in the processing capabilities of the two extrusion modes as screw designs can be designed for either mode to accomplish a wide range of pressure and shear profiles....
[...]
TL;DR: Overall, the films fabricated from polymer-based suspensions at higher viscosity dried at different conditions exhibited similar mechanical properties, improved drug content uniformity, and achieved fast drug dissolution.
48 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...In HME, drug is mixed with a polymer and then both are elted and extruded through an orifice or die (Crowley et al., 2007; epka et al., 2003, 2005), typically resulting in amorphous form....
[...]
...In HME, drug is mixed with a polymer and then both are elted and extruded through an orifice or die (Crowley et al., 2007; epka et al., 2003, 2005), typically resulting in amorphous form....
[...]
References
More filters
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