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: It is summarized that the addition of acidified HP biopolymer increased the bioaccessibility, functionality, and improved the physicochemical properties of nutraceutical compounds in the extrudate AGN formulation.
Abstract: Angelica gigas Nakai (AGN) is a popular traditional herbal medicine which has been used to alleviate various human diseases in Korea since ancient times. However, the low bioaccessibility of the nutraceutical compounds of AGN results in a poor water solubility, thereby limiting bioavailability. In this regard, a ternary AGN-biopolymer-plasticizer composite (AGNC) was developed to enhance the bioaccessibility of nutraceutical compounds from extrudate AGN formulations manufactured by hot melt extrusion (HME). The AGNC was prepared with extrudate AGN (EAGN) using different hydroxypropyl methylcellulose (HPMC) biopolymers (5% w/w) viz.: hypromellose phthalate (HP), hypromellose (AN), and hypromellose (CN) along with acetic acid (AA) (0.1 M, 20% w/v) as a plasticizer. The non-extrudate fresh AGN (FAGN) powder was used as a control. The physicochemical properties of the extrudate formulations and control were characterized by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). DSC analysis showed a lower enthalpy (ΔH) (12.22 J/g) and lower glass transition temperature (Tg) (41 °C) in HP-AA-EAGN compared to the control. FTIR confirmed the physical crosslinking between AGN and biopolymer in the extrudate composite and demonstrated that some functional groups formed viz., -OH and -CH2. The obtained result also shows that the particle size was reduced by 341 nm, and solubility was increased by 65.5% in HP-AA-EAGN compared to the control (1499 nm, 29.4%, respectively). The bioaccessibility of the total phenolic content and the total flavonoids-including decursin (D) and decursinol angelate (DA)-were significantly higher in HP-AA-EAGN compared to the control. The 2,2-diphenyl-1 picryl hydrazyl (DPPH) free radical scavenging capacity and ferric reducing antioxidant power assay (FRAP) indicated that the HP-AA-EAGN formulation preserves a greater antioxidant profile than the other formulations. Finally, it is summarized that the addition of acidified HP biopolymer increased the bioaccessibility, functionality, and improved the physicochemical properties of nutraceutical compounds in the extrudate AGN formulation.
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Cites background from "Pharmaceutical Applications of Hot-..."
...The enhanced aqueous solubility of the active compound is achieved by the amorphization of its crystalline compounds, using hydrophilic polymers through hot melt extrusion by steric hindrance and non-covalent bonding within the polymeric chain [12]....
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TL;DR: This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.
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TL;DR: In this paper, a review of hot-melt extrusion-based solid dispersion formulations of poorly water-soluble drugs is presented, where various factors, including polymers, drug properties, additives and surfactants, are discussed.
8 citations
11 Nov 2015
TL;DR: A group of clinicians and scientists with a common interest in pediatric drug development and medicines-use systems developed a practical framework for identifying a list of active pharmaceutical ingredients (APIs) with the greatest market potential for development to use in pediatric patients.
Abstract: The lack of commercially-available pediatric drug products and dosage forms is well-known. A group of clinicians and scientists with a common interest in pediatric drug development and medicines-use systems developed a practical framework for identifying a list of active pharmaceutical ingredients (APIs) with the greatest market potential for development to use in pediatric patients. Reliable and reproducible evidence-based drug formulations designed for use in pediatric patients are needed vitally, otherwise safe and consistent clinical practices and outcomes assessments will continue to be difficult to ascertain. Identification of a prioritized list of candidate APIs for oral formulation using the described algorithm provides a broader integrated clinical, scientific, regulatory, and market basis to allow for more reliable dosage forms and safer, effective medicines use in children of all ages. Group members derived a list of candidate API molecules by factoring in a number of pharmacotherapeutic, scientific, manufacturing, and regulatory variables into the selection algorithm that were absent in other rubrics. These additions will assist in identifying and categorizing prime API candidates suitable for oral formulation development. Moreover, the developed algorithm aids in prioritizing useful APIs with finished oral liquid dosage forms available from other countries with direct importation opportunities to North America and beyond.
8 citations
TL;DR: In this paper, the authors examined the swelling behavior in the release medium of hot-melt extruded starch-based pellets and concluded that the drug release mechanism of wx corn starch pellets is almost solely based on erosion.
Abstract: Hot-melt extrusion with die-face pelletisation is an excellent technique to continuously produce almost monodisperse spherical starch pellets. For a better understanding of drug release mechanisms from hot-melt extruded starch-based pellets the swelling behaviour in the release medium was examined by reflected-light microscopy. From the microscopic images it can be concluded that the drug release mechanism of wx corn starch pellets is almost solely based on erosion. The release mechanism of corn starch, pea starch and potato starch pellets is primarily a swelling-based process. Although the release mechanism of a swelling dosage form is theoretically complex, it was found that the fractional drug release from the hot-melt extruded starch pellets can be described with the Noyes–Whitney equation. This facilitates the evaluation of the influence of the physicochemical properties of the matrix and the chemical properties of the active ingredient on the drug release rate. It was found that pellet size, porosity and velocity with which the penetrant diffuses into the pellet-core the water solubility of the drug as well as the molecular structure and composition of the starches are the main factors influencing drug release from the swelling starch pellets.
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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