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: The potential advantages of hot-melt extrusion over direct compression for the processing of soft drug granules coated with Eudragit(®) L polymer were demonstrated.
39 citations
TL;DR: The solubility and in vitro dissolution performance of both drugs in SD formulations was improved significantly when compared with pure drugs and marketed product while the in vivo studies revealed the same.
39 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...…of administration of non-compatible drugs, modulation of drug release, reduction of dose dumping (Repka et al., 2007a), ease of dose adjustment (Repka et al., 2007b) and increase patient compliance for fixed dose combination formulation over traditional pharmaceutical processing systems…...
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...Moreover, it has advantages of administration of non-compatible drugs, modulation of drug release, reduction of dose dumping (Repka et al., 2007a), ease of dose adjustment (Repka et al., 2007b) and increase patient compliance for fixed dose combination formulation over traditional pharmaceutical…...
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TL;DR: Developing a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME) and FTIR spectroscopy revealed the interaction between drug and polymers.
Abstract: The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.
39 citations
TL;DR: Degassing considerably reduced the post-extrusion moisture content of Formula D3, which contains the highly hygroscopic polymer Kollidon® 17 PF, suggesting that the greatest influence of this process is on hyGroscopic materials.
39 citations
TL;DR: ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption.
Abstract: Amorphous solid dispersions (ASDs) improve the oral delivery of poorly water-soluble drugs. ASDs of olanzapine (OLZ), which have a high melting point and low solubility, are performed using a complicated process. Three-dimensional (3D) printing based on hot-melt pneumatic extrusion (HMPE) is a simplified method for producing ASDs. Unlike general 3D printing, printlet extrusion is possible without the preparation of drug-loaded filaments. By heating powder blends, direct fused deposition modeling (FDM) printing through a nozzle is possible, and this step produces ASDs of drugs. In this study, we developed orodispersible films (ODFs) loaded with OLZ as a poorly water-soluble drug. Various ratios of film-forming polymers and plasticizers were investigated to enhance the printability and optimize the printing temperature. Scanning electron microscopy (SEM) showed the surface morphology of the film for the optimization of the polymer carrier ratios. Differential scanning calorimetry (DSC) was used to evaluate thermal properties. Powder X-ray diffraction (PXRD) confirmed the physical form of the drug during printing. The 3D printed ODF formulations successfully loaded ASDs of OLZ using HMPE. Our ODFs showed fast disintegration patterns within 22 s, and rapidly dissolved and reached up to 88% dissolution within 5 min in the dissolution test. ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption. Moreover, this new technology showed prompt fabrication feasibility of various formulations and ASD formation of poorly water-soluble drugs as a single process. The immediate dissolution within a few minutes of ODFs with OLZ, an atypical antipsychotic, is preferred for drug compliance and administration convenience.
38 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