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 objective of the present review article is to present the current status of in vitro drug release testing of IVRs and to critically discuss current compendial and non-official in vitrodrug release methods with regard to their discriminatory power and in vivo predictivity.
Abstract: The vagina is a promising site for both local and systemic drug delivery and represents an interesting administration route for compounds with poor oral bioavailability. Whereas most of the currently marketed dosage forms were designed as immediate release formulations, intravaginal rings (IVRs) offer the possibility of a controlled vaginal drug delivery over several weeks or months. For a long time, the development of IVRs was limited to steroid-releasing formulations. Recently, IVRs have witnessed a surge of new interest as promising delivery systems for microbicides. Therefore, various novel IVR designs have been introduced. To ensure that only safe and effective IVRs will be administered to patients, it is important to properly distinguish between IVRs with desired and undesired release performance. In vitro methods for evaluating drug release of IVRs that present with sufficient predictive capacity for in vivo drug release, and discriminatory power with regard to IVRs quality, are an essential tool for this purpose. The objective of the present review article is to present the current status of in vitro drug release testing of IVRs and to critically discuss current compendial and non-official in vitro drug release methods with regard to their discriminatory power and in vivo predictivity.
14 citations
TL;DR: It is illustrated that the proper utilization of drug hydrates can significantly improve the processability of HME for preparing ASDs, and the dehydration of CBZ dihydrate resulted in a disordered state of the drug molecule.
Abstract: Amorphous solid dispersions (ASDs) are commonly used in the pharmaceutical industry to improve the dissolution and bioavailability of poorly water-soluble drugs. Hot melt extrusion (HME) has been employed to prepare ASD based products. However, due to the narrow processing window of HME, ASDs are normally obtained with high processing temperatures and mechanical stress. Interestingly, one-third of pharmaceutical compounds reportedly exist in hydrate forms. In this study, we selected carbamazepine (CBZ) dihydrate to investigate its solid-state changes during the dehydration process and the impact of the dehydration on the preparation of CBZ ASDs using a Leistritz micro-18 extruder. Various characterization techniques were used to study the dehydration kinetics of CBZ dihydrate under different conditions. We designed the extrusion runs and demonstrated that: 1) the dehydration of CBZ dihydrate resulted in a disordered state of the drug molecule; 2) the resulted higher energy state CBZ facilitated the drug solubilization and mixing with the polymer matrix during the HME process, which significantly decreased the required extrusion temperature from 140 to 60 °C for CBZ ASDs manufacturing compared to directly processing anhydrous crystalline CBZ. This work illustrated that the proper utilization of drug hydrates can significantly improve the processability of HME for preparing ASDs.
14 citations
Cites background from "Pharmaceutical Applications of Hot-..."
...HME process provides mechanical energy (shear and pressure) [11] and thermal energy (heat transfer) [12] to enable the melting of the drug and polymer, particle size reduction, mixing between components, and forming of the extrudates [13,14]....
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TL;DR: The main objectives of this work were to develop and characterize new 3D printing filaments and print them directly onto a packaging material, which can take us one step closer to the production of personalized drugs in pharmacies.
14 citations
TL;DR: This review provides discussions of the FDC application in variety of disease using various formulation technologies that consider characteristics of each active pharmaceutical ingredient (API) in FDC to maximize the benefits and overcome the challenges of developing FDC products.
Abstract: Fixed dose combination (FDC) products are common in the treatment of various disease such as hypertension, diabetes, HIV and HCV, Pain, Respiratory disease for improving therapeutic efficacy and tolerability. They make it possible to combine more than two drug molecules with optimal doses, dosage form and optimize the treatment. This review provides discussions of the FDC application in variety of disease. various formulation technologies such as bilayer system, active film coating, co-crystal, multi-particulate system, Hot-melt co-extrusion, hot fusion method, spray drying and 3D-printing that consider characteristics of each active pharmaceutical ingredient (API) in FDC to maximize the benefits and overcome the challenges of developing FDC products. FDC has utilized as a promising dosage form to increase the oral absorption of drugs. From beneficial perspective, they offer efficacy and safety improvement, product exclusivity, patient compliance, medicinal cost reduction. while disadvantage perspectives such as a lack of dose flexibility, drug interaction, difference dosage regimen, dose difference and difference of physicochemical properties should be considered for the use of FDC, differences in individual drug characteristics, drug release profiles, therapeutic dose, and solubility should be considered for FDCs design and formulation.
13 citations
01 Jan 2011
13 citations
Cites background or methods from "Pharmaceutical Applications of Hot-..."
...Pressure inside the barrel is generated by melting and mixing viscous materials, and pumping them through a die (Luker 2003; Crowley et al. 2007)....
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...It has been afterward applied in the field of pharmaceutical industry (Crowley et al. 2007)....
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...The polymer carriers, which are PLGA or PLA for biodegradable implants, are molten and act as a thermal binder (Crowley et al. 2007)....
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...(Crowley et al. 2007)....
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...It can be an effective method to use for improving bioavailability of poorly water-soluble drugs by an increase in drug solubility (Breitenbach 2002; Mollan 2003; Crowley et al. 2007; Repka et al. 2007)....
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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