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: A systematic study of miscibility and extrudability of drug-polymer mixtures by rheological and torque analysis as a function of temperature will help formulators select optimal melt extrusion processing conditions to develop solid dispersions.
46 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...HME has many advantages over other technologies used for solid dispersion (Crowley et al., 2007; Ghosh et al., 2012; Shah et al., 2013; Lakshman et al., 2008)....
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TL;DR: The results indicate that hot-melt extrusion is a viable technique for the preparation of DOM buccal-adhesive controlled release films with improved bioavailability by CCD.
Abstract: Objective: The aim of the present investigation was the development and in vivo characterization of domperidone (DOM) hot-melt extruded (HME) controlled release films by central composite design (CCD) for buccal delivery.Methods: Concentration of PEO N750 (X1) and HPMC E5 LV (X2) as independent variables and tensile strength (Y1), percent drug release at 6 h (Q6, Y2) and percent drug permeated at 6 h (Y3, P6) as responses. In total, 13 formulations were prepared and studied. HME films were evaluated for drug excipient compatibility, physico-mechanical properties, drug content, in vitro drug release, bioadhesion, swelling and erosion, ex vivo permeation. Furthermore, statistically optimized formulation was subjected for bioavailability studies in healthy human volunteers.Results: Statistically optimized formulation exhibited a tensile strength (3.86 kg/mm2), 93.62 ± 2.84% of drug release and 63.36 ± 2.12% of drug permeated in 6 h. HME films demonstrated no drug excipient interaction and excellent c...
46 citations
Cites methods from "Pharmaceutical Applications of Hot-..."
...Drug Dev Ind Pharm, 2016; 42(3): 473–484...
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...The concentration of PEO shows marginal effect on the drug release and permeation, but HPMC had the positive effect on the permeation (+0.26 from Equation (6) the value of) of drug from films....
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...The relative bioavailability (F) for buccal delivery was calculated using Equation (3)....
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...Swelling index (SI) and weight loss were determined gravimetrically according to the following Equations (1) and (2) Swelling index ¼ wet weight original dry weight original dry weight 100, ð1Þ Erosion ð%Mass lossÞ ¼ original weight remaining dry weight original weight 100: ð2Þ Ex vivo drug permeation Ex vivo permeation of DOM from the each and statistically optimized HME CR film was studied across the porcine buccal membrane using Franz diffusion cell....
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TL;DR: SME is a critical parameter for predicting enhanced dissolution and physical stability of IND in ASDs and multi‐nuclear and multi-dimensional ssNMR provide mechanistic understanding of molecular properties and bring new perspectives for preparation, analysis, and applications of XDP as a pharmaceutical carrier.
46 citations
Patent•
21 Nov 2011TL;DR: Salts and crystalline forms of 4-(4{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1yl]methyl}piperazin-1]-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-sulfonyl)-2-(1H-polypyrrolo[2,3-b]pyridin-5-yloxy)benzamide
Abstract: Salts and crystalline forms of 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide are suitable active pharmaceutical ingredients for pharmaceutical compositions useful in treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.
45 citations
TL;DR: Modulation of the microenvironmental pH to an acidic range via incorporation of citric acid in PEO-plasticizer matrices significantly improved the stability of the prodrug, with almost 90% of the theoretical drug remaining as opposed to only 15% remaining in Poe-only matrices when stored at 40 degrees C for up to 3 months.
45 citations
Cites background or methods from "Pharmaceutical Applications of Hot-..."
...These agents lower the glass transition temperature and hence the melt viscosity of the polymer and allow the hot-melt processing to be performed at a lower temperature, thereby improving the processing stability of both the polymer and the drug [19]....
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...For fabrication of polymeric matrices by a hot-melt method, a processing temperature of at least 20–50 C above the melting temperature of semi-crystalline polymer or glass transition temperature of an amorphous polymer is desirable to lower the polymer melt viscosity [19]....
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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