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
Dissertation•
01 Jan 2016
TL;DR: In this article, the effect of glass composition on the rheological and thermo-chemical properties and nano/microstructure of these new materials, focusing on the tin fluoride (SnF2) content in the glasses, was investigated.
Abstract: The blending of polymers is a relatively inexpensive method of manipulating their properties
and is common practice in the industry. Phosphate glass/polymer hybrids are an emerging
class of nanomaterial with peculiar characteristics derived from nano-micro interactions of
their components. Inorganic phosphate glasses are made up of chain-like molecules and are
similar to polymer chains in their structure. These glasses are also unique in exhibiting
similar processing temperatures to polymers, which opens up the possibility of co-processing
and of greatly extending the range of obtainable properties. Both components being fluid
during processing allow controlling and tailoring hybrid morphologies, and avoiding the
problem of the intractable viscosity inherent from a high solid filler concentration. This work
investigates the blending of an organic semi-crystalline polymer, polyamide 11 (PA 11), with
different compositions of phosphate glasses. Experimental and theoretical studies of
miscibility and phase behaviour of these unusual blends were analysed. In particular the
research investigated the effect of glass composition on the rheological and thermo-chemical
properties and nano/microstructure of these new materials, focusing on the tin fluoride (SnF2)
content in the glasses. The Flory Huggins equilibrium depression point model was employed
to correlate and predict miscibility behaviour in these new systems. The experimental results
showed that a high amount of SnF2 could act as a proper compatibilizer for the novel Rilsan
® PA 11 matrix. Experiments showed that the halogen content lowered the glass transition
temperature (Tg) and softening point (Ts) of the glasses, allowing both phases being fluid
during melt-blending. However the water stability of the glasses was improved with
increasing SnF2 content in the network. The particle size of glass in the hybrids was inversely
correlated with SnF2 in the glass composition. This phenomenon resulted in lowering the
equilibrium melting point (Tm0
) in the hybrids. The load force (F) generated during the
extrusion process and the hybrid viscosities decreased, without compromising chemical and
thermal stability of the materials. The Tg of PA 11, measured as shifts of the major peak in
dissipation factor against temperature plot, was inversely correlated with SnF2 content in the glass composition, phenomenon often attributed to the partial miscibility of components in a
system. The stiffness of the hybrid was improved by higher amount of SnF2 in the glass
compositions with polyamide reinforced by the glass having the lowest Tg (60 SnF2 mol%).
The longitudinal storage modulus was inversely correlated with temperature for PA 11 and
all hybrids and increased with melting each phosphate glass with the polymer matrix. The
storage modulus increased with SnF2 content in the glass composition in the matrix at lower
temperature and reached a constant value for all hybrids at higher temperature. The viscosity
and shear modulus decreased and increased respectively with increasing angular frequency.
Shear modulus of polyamide matrix was lowered by each phosphate glass. All samples
showed a small upturn in the modulus versus angular frequency curve at the lowest
viscosities, behaviour related to the presence of yield stress in the hybrids, more evident in
the hybrids with the highest content of SnF2 in the glass.
1 citations
Dissertation•
01 Jan 2015
TL;DR: In this article, the authors proposed a method to reduce the size of particles by using Rapid Expansion of Supercritical Solution (RESS) and showed the properties of the extrusion process.
Abstract: ............................................................................................................ 19 Resumo............................................................................................................. 23 Abbreviations .................................................................................................... 29 List of tables ...................................................................................................... 31 List of figures ..................................................................................................... 33 List of publications ............................................................................................. 37 THESIS ........................................................................................................... 39 1. Challenges ............................................................................................ 41 2. Motivation and aim................................................................................. 41 3. Hypothesis ............................................................................................. 42 4. Research objectives and outcomes ....................................................... 42 5. Organization of the thesis ...................................................................... 43 CHAPTER 1.................................................................................................... 45 Introduction ................................................................................................... 45 1.1. Reduction of the size of particles ........................................................ 47 1.1.1. Top-down approaches .................................................................. 47 1.1.2. Bottom-up approaches .................................................................. 48 1.1.2.1. Supercritical fluids techniques ................................................. 48 1.2. Rapid expansion of supercritical solutions (RESS) ............................. 49 1.2.1. Concept ........................................................................................ 49 1.2.2. Solvents used in RESS ................................................................. 50 1.2.3. Particle formation .......................................................................... 50 1.2.4. Process parameters influencing the properties of the particles ..... 51 1.3. Extrusion and co-extrusion ................................................................. 52 Production of laminar extrudates containing particles of a model drug processed by supercritical fluids 12 1.3.1. Applications .................................................................................. 52 1.3.2. Types of extrusion......................................................................... 53 1.3.2.1. Wet extrusion .......................................................................... 53 1.3.2.2. Solvent-free extrusion and solid lipid extrusion ........................ 53 1.3.2.3. Hot-melt extrusion ................................................................... 54 1.3.2.4. Cold extrusion ......................................................................... 54 1.3.2.5. Discontinuous extrusion .......................................................... 55 1.3.2.6. Continuous extrusion ............................................................... 55 1.3.3. Extruders ...................................................................................... 55 1.3.4. Shapes of extrudates .................................................................... 56 1.3.5. Materials for extrusion ............................................................. 56 1.3.5.1. Materials for extrusion at room temperature, in the absence of solvents ................................................................................ 58 1.3.5.2. Formulations for extrusion ....................................................... 58 1.3.6. Process of extrusion and co-extrusion .......................................... 59 1.3.6.1. Operational parameters and equipment features ..................... 59 1.3.6.2. Characterizing the extrusion process (extrusion profiles) ......... 60 1.3.6.3. Other manufacturing operations involved ................................ 61 1.3.7. Characterization and properties of extrudates and co-extrudates .. 62 1.3.7.1. Surface .................................................................................... 62 1.3.7.2. Thickness ................................................................................ 63 1.3.7.3. Density and porosity ................................................................ 63 1.3.7.4. Mechanical properties ............................................................. 63 1.3.7.5. Thermal behavior .................................................................... 64 1.3.8. Further processing of extrudates ................................................... 64 1.4. Model drugs ....................................................................................... 66 1.4.1. Coumarin ...................................................................................... 66 Production of laminar extrudates containing particles of a model drug processed by supercritical fluids 13 1.4.2. Levothyroxine (free acid) .............................................................. 66 CHAPTER 2.................................................................................................... 67 Characterization of coumarin particles micronized by the rapid expansion of supercritical solutions (RESS) technique ............................ 67 2.
1 citations
01 Jan 2015
TL;DR: In this article, the KINETICS of DRUG DISSOLUTION in POLYMERS DURING HOT-MELT EXTRUSION is described.
Abstract: THE KINETICS OF DRUG DISSOLUTION IN POLYMERS DURING HOT-MELT EXTRUSION
1 citations
Additional excerpts
...(Crowley, 2007)....
[...]
TL;DR: In vivo experiments with rats demonstrated that the optimized hot-melt extruded formulation was absorbed more rapidly with lower deviation and regardless of the meal consumed when compared to marketed cilostazol formulations.
Abstract: The aim of this study was to control the dissolution rate and permeability of cilostazol. To enhance the dissolution rate of the active pharmaceutical ingredient (API), hot-melt extrusion (HME) technology was applied to prepare a solid dispersion (SD). To control permeability in the gastrointestinal tract regardless of food intake, the HME process was optimized based on physiologically based pharmacokinetic (PBPK) simulation. The extrudates were produced using a laboratory-scale twin-screw hot-melt extruder with co-rotatory screws and a constant feeding rate. Next, for PBPK simulation, parameter-sensitive analysis (PSA) was conducted to determine the optimization approach direction. As demonstrated by the dissolution test, the solubility of extrudate was enhanced comparing cilostazol alone. Based on the PSA analysis, the surfactant induction was a crucial factor in cilostazol absorption; thus, an extrudate with an even distribution of lipids was produced using hot-melt extrusion technology, for inducing the bile salts in the gastrointestinal tract. In vivo experiments with rats demonstrated that the optimized hot-melt extruded formulation was absorbed more rapidly with lower deviation and regardless of the meal consumed when compared to marketed cilostazol formulations.
1 citations
23 Oct 2019
1 citations
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