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: In this article , the critical cooling rate of amorphous solid dispersions (ASDs) was determined through the time-temperature-transformation (TTT) diagram.
Abstract: The critical cooling rate (CRcrit) to prevent drug crystallization during the preparation of nifedipine amorphous solid dispersions (ASDs) was determined through the time-temperature-transformation (TTT) diagram. ASDs were prepared with polyvinylpyrrolidone, hydroxypropylmethyl cellulose acetate succinate, and poly(acrylic acid). ASDs were subjected to isothermal crystallization over a wide temperature range, and the time and temperature dependence of nifedipine crystallization onset time (tC) was determined by differential scanning calorimetry (DSC) and synchrotron X-ray diffractometry. TTT diagrams were generated for ASDs, which provided the CRcrit for the dispersions prepared with each polymer. The observed differences in CRcrit could be explained in terms of differences in the strength of interactions. Stronger drug-polymer interactions led to longer tC and decreased CRcrit. The effect of polymer concentrations (4-20% w/w) was also influenced by the strength of the interaction. The CRcrit of amorphous NIF was ∼17.5 °C/min. Addition of 20% w/w polymer resulted in a CRcrit of ∼0.05, 0.2, and 11 °C/min for the dispersions prepared with PVP, HPMCAS, and PAA, respectively.
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TL;DR: Solid-dispersions have been and continue to be one of the key technologies for solving the issue of poor solubility for newer hydrophobic molecules which are being discovered and would give a new lease of life for such drugs enabling them to be delivered in an effective way.
Abstract: Objective: This review article explores solid dispersions (SDs) as one of the suitable approaches to formulate poorly water-soluble drugs. The objective of this review on SD techniques is to explore their utility as a feasible, simple, and economically viable method for augmentation of dissolution of hydrophobic drugs.
Methods: Various types of SDs are classified and compared. Use of surfactants to stabilize the SDs and their potential advantages and disadvantages has been discussed. Different techniques for preparing and evaluating SDs are appraised along with discussions on scalability and industrial production. Review of the current research on SD along with future trends is also offered.
Results: Based on the various researches, SDs offer an efficient means of improving bioavailability while concurrently contributing to lower toxicity and dose-reduction.
Conclusion: Solid-dispersions have been and continue to be one of the key technologies for solving the issue of poor solubility for newer hydrophobic molecules which are being discovered. This would give a new lease of life for such drugs enabling them to be delivered in an effective way.
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Cites background from "Pharmaceutical Applications of Hot-..."
...HME is enormously adaptable for making industrial-scale SD [33]....
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16 Jan 2015
TL;DR: This bachelor thesis is concerned on review of polymeric materials, which are used for the production of bone implants, their mechanical and biological properties, methods of production and vitality of the patient's body.
Abstract: This bachelor thesis is concerned on review of polymeric materials, which are used for the production of bone implants. At the beginning of thesis are generally described biomaterials and technical terms associated with this issue. Next part of thesis deals with causes leading to replacement of bone with bone fillers or implants and interaction of bone replacemnt with organism, including risks affecting their functionality. The last part of thesis is focused in the most important absorbable and non-absorbable polymerics materials, their mechanical and biological properties, methods of production and vitality of the patient's body.
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TL;DR: The use of a 16 mm twin screw extruder as a platform technology for solid feeds is investigated using four solid pharmaceutical ingredients (PI) in a mixture of water and IPA to gain further scientific understanding on dissolution kinetics and to compare kinetics in both a batch and continuous system.
Abstract: The introduction of continuous manufacturing of pharmaceuticals has highlighted the challenging area of continuous dissolution of solids for work ups to flow chemistry systems. In this stud...
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10 Dec 2013
TL;DR: In this article, a methode originale for determining efficacement la solubilite des PA dans les polymeres is presented. But this methode is not applicable to the case of polymers.
Abstract: La dispersion moleculaire d’un principe actif (PA) dans un polymere est generalement utilisee pour accroitre a la fois la solubilite et la stabilite physique de sa forme amorphe. Cependant, ce type de formulation demande une parfaite connaissance de la solubilite du PA dans le polymere. Cependant, les methodes actuelles pour determiner les courbes de solubilite sont longues et fastidieuses a mettre en oeuvre. Dans cette these, nous presentons une methode originale pour determiner efficacement la solubilite des PA dans les polymeres. L’originalite de cette methode reside dans le fait que les etats d’equilibre satures sont ici atteints par demixtion d’une solution solide amorphe sursaturee en PA et non par la methode classique de dissolution du PA cristallin au sein du polymere amorphe. Les etats d’equilibre satures sont donc beaucoup plus rapides a atteindre en raison de la mobilite moleculaire accrue resultant de la forte plastification du polymere imposee par les conditions de sursaturation. Nous avons aussi teste la possibilite de predire les courbes de solubilite par des methodes numeriques ab-initio (par dynamique moleculaire et methodes quantiques). Les methodes experimentales et numeriques ont ete validees en etudiant des systemes polymere/PA dont les courbes de solubilite ont deja ete determinees par des methodes classiques. Les systemes etudies sont : PVPK12/indometacine, PVPK30/griseofulvine et β-cyclodextrine methylee/griseofulvine. Les techniques d’investigations utilisees sont esentiellement l’analyse enthalpique differentielle a balayage (DSC) et la diffraction des rayons X sur poudre (DRX).
1 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...C'est le cas par exemple de KinetiSol® (une technologie par fusion [11, 12]) ou des procédés d'extrusion à chaud [13]....
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References
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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
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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
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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
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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