Preparation And Characterization Of Carvedilol And Indomethacin Amorphous Solid Dispersions
Download Preparation And Characterization Of Carvedilol And Indomethacin Amorphous Solid Dispersions full books in PDF, epub, and Kindle. Read online free Preparation And Characterization Of Carvedilol And Indomethacin Amorphous Solid Dispersions ebook anywhere anytime directly on your device. Fast Download speed and no annoying ads. We cannot guarantee that every ebooks is available!
| Author | : Alena Duszová |
| Publisher | : |
| Total Pages | : 148 |
| Release | : 2019 |
| Genre | : |
| ISBN | : |
Amorphous solid dispersions provide one of the few approaches available for improving the solubility of poorly water-soluble active pharmaceutical ingredients. They are mainly 2-component systems consisting of drug and polymer, where the amorphous drug is molecularly dispersed in an amorphous polymer matrix. The presence of polymer helps to maintain the drug in an amorphous state, which is thermodynamically unstable due to the possession of excess Gibbs free energy, enthalpy and entropy. To delay or prevent crystallization, the molecular mobility of the amorphous glass should be sufficiently low to avoid nuclei formation and crystal growth and is achieved by the maintaining the amorphous solid dispersion at a specific storage temperature and conditions, together with strong drug-polymer interactions. One of the major preparation processes for amorphous solid dispersions involves hot melt extrusion, producing solid dispersions at elevated temperatures without solvents. Four amorphous solid dispersions of 20% and 40% (w/w) carvedilol and indomethacin were manufactured using HPMC-AS as a polymeric carrier. Solid dispersions were characterized as freshly manufactured powders, as they were during a 1-month stability study using various analytical methods. Attention was paid to the molecular interactions in solid dispersions, miscibility, phase separation, crystallinity and molecular mobility. Solid dispersions of carvedilol exhibited satisfactory stability, which was reflected in preservation of amorphous carvedilol due to the sufficiently high glass transition temperature of the solid dispersions and the drug-polymer interactions. Indomethacin solid dispersions demonstrated the importance of drug loading in solid dispersions, together with the moderate or weak intermolecular interactions between drug and polymer. The enthalpy relaxation provides information regarding the lower molecular mobility of carvedilol in solid dispersions, indicating sufficient stabilization of amorphous drug by the selected polymer. Moreover, the intermolecular interactions were studied below and higher than the glass transition of the mixtures with different drug loadings, using temperature-dependent infrared spectroscopy. During this experiment, it was found that the intermolecular hydrogen bonds varied with the composition and measured temperature, resulting in disruption of intermolecular hydrogen bonds after passing the glass transition temperature.
| Author | : Vishak Sridhar |
| Publisher | : |
| Total Pages | : 181 |
| Release | : 2013 |
| Genre | : |
| ISBN | : |
The objective of this project was to improve the solubility of two poorly water soluble drugs, namely indomethacin and phenytoin by formulating ternary solid dispersions with a carrier and an adsorbent. Urea was used as the dispersing agent for indomethacin, while Kollidon®VA64 was used for both indomethacin and phenytoin. Solid dispersions with urea and indomethacin were prepared by the hot melt method while the ones with Kolllidon®VA64 were prepared by the solvent extraction method. Various techniques were used to characterize the solid dispersions, immediately after they were made and after two months of elevated temperature and relative humidity, including Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction (PXRD), Scanning Electron Microscopy (SEM) and in vitro dissolution studies. The DSC data showed thermograms for all the ingredients, physical mixtures and solid dispersions. It indicated that the physical mixtures tend to have the drugs in their crystalline form. However, the solid dispersions gave formulations that were completely amorphous. PXRD studies confirmed these results. PXRD results for the drugs show their crystalline nature which could not be seen with the solid dispersions. It also confirmed that the formulations were stable over the two month period when they were kept at elevated temperature and controlled relative humidity conditions. SEM images indicated that the solid dispersion of the drug and carrier were coated on the Nuesilin®US2 well, showing it was possible to coat the solid dispersion on the Nuesilin®US2 by both the fusion method and solvent extraction method . In vitro dissolution studies reveal that there is an increase in both the quantity of drug solubilized and the rate of dissolution after formulation into their solid dispersions. The stability studies for two months under various temperatures (300C, 350C, 400C, and 450C) and relative humidity conditions (100%, 75.29 ±0.12%, 54.38 ±0.23 and 23.11 ±0.25% RH) indicated that the formulations might be stable. It also indicated that as the quantity of drug in the formulations increased, there was a tendency for some formulations to be unstable. The accelerated stability studies also helped to determine the trends with the shelf life of the formulations using the Arrhenius equation. It also gave some idea about the tendency of relative humidity to affect the degradation rate of the drug.
| Author | : Navnit Shah |
| Publisher | : Springer |
| Total Pages | : 702 |
| Release | : 2014-11-21 |
| Genre | : Medical |
| ISBN | : 1493915983 |
This volume offers a comprehensive guide on the theory and practice of amorphous solid dispersions (ASD) for handling challenges associated with poorly soluble drugs. In twenty-three inclusive chapters, the book examines thermodynamics and kinetics of the amorphous state and amorphous solid dispersions, ASD technologies, excipients for stabilizing amorphous solid dispersions such as polymers, and ASD manufacturing technologies, including spray drying, hot melt extrusion, fluid bed layering and solvent-controlled micro-precipitation technology (MBP). Each technology is illustrated by specific case studies. In addition, dedicated sections cover analytical tools and technologies for characterization of amorphous solid dispersions, the prediction of long-term stability, and the development of suitable dissolution methods and regulatory aspects. The book also highlights future technologies on the horizon, such as supercritical fluid processing, mesoporous silica, KinetiSol®, and the use of non-salt-forming organic acids and amino acids for the stabilization of amorphous systems. Amorphous Solid Dispersions: Theory and Practice is a valuable reference to pharmaceutical scientists interested in developing bioavailable and therapeutically effective formulations of poorly soluble molecules in order to advance these technologies and develop better medicines for the future.
| Author | : Marzena Rams-Baron |
| Publisher | : Springer |
| Total Pages | : 234 |
| Release | : 2018-02-09 |
| Genre | : Science |
| ISBN | : 3319720023 |
This book explains theoretical and technological aspects of amorphous drug formulations. It is intended for all those wishing to increase their knowledge in the field of amorphous pharmaceuticals. Conversion of crystalline material into the amorphous state, as described in this book, is a way to overcome limited water solubility of drug formulations, in this way enhancing the chemical activity and bioavailability inside the body. Written by experts from various fields and backgrounds, the book introduces to fundamental physical aspects (explaining differences between the ordered and the disordered solid states, the enhancement of solubility resulting from drugs amorphization, physical instability and how it can be overcome) as well as preparation and formulation procedures to produce and stabilize amorphous pharmaceuticals. Readers will thus gain a well-funded understanding and find a multi-faceted discussion of the properties and advantages of amorphous drugs and of the challenges in producing and stabilizing them. The book is an ideal source of information for researchers and students as well as professionals engaged in research and development of amorphous pharmaceutical products.
| Author | : Ann Newman |
| Publisher | : John Wiley & Sons |
| Total Pages | : 502 |
| Release | : 2015-03-09 |
| Genre | : Science |
| ISBN | : 1118455207 |
Providing a roadmap from early to late stages of drug development, this book overviews amorphous solid dispersion technology – a leading platform to deliver poorly water soluble drugs, a major hurdle in today’s pharmaceutical industry. • Helps readers understand amorphous solid dispersions and apply techniques to particular pharmaceutical systems • Covers physical and chemical properties, screening, scale-up, formulation, drug product manufacture, intellectual property, and regulatory considerations • Has an appendix with structure and property information for polymers commonly used in drug development and with marketed drugs developed using the amorphous sold dispersion approach • Addresses global regulatory issues including USA regulations, ICH guidelines, and patent concerns around the world
| Author | : Rolf Hilfiker |
| Publisher | : John Wiley & Sons |
| Total Pages | : 618 |
| Release | : 2019-01-04 |
| Genre | : Science |
| ISBN | : 3527697853 |
"Polymorphism in the Pharmaceutical Industry - Solid Form and Drug Development" highlights the relevance of polymorphism in modern pharmaceutical chemistry, with a focus on quality by design (QbD) concepts. It covers all important issues by way of case studies, ranging from properties and crystallization, via thermodynamics, analytics and theoretical modelling right up to patent issues. As such, the book underscores the importance of solid-state chemistry within chemical and pharmaceutical development. It emphasizes why solid-state issues are important, the approaches needed to avoid problems and the opportunities offered by solid-state properties. The authors include true polymorphs as well as solvates and hydrates, while providing information on physicochemical properties, crystallization thermodynamics, quantum-mechanical modelling, and up-scaling. Important analytical tools to characterize solid-state forms and to quantify mixtures are summarized, and case studies on solid-state development processes in industry are also provided. Written by acknowledged experts in the field, this is a high-quality reference for researchers, project managers and quality assurance managers in pharmaceutical, agrochemical and fine chemical companies as well as for academics and newcomers to organic solid-state chemistry.
| Author | : Christoph Schick |
| Publisher | : Springer |
| Total Pages | : 796 |
| Release | : 2016-06-28 |
| Genre | : Technology & Engineering |
| ISBN | : 3319313290 |
In the past decades, the scan rate range of calorimeters has been extended tremendously at the high end, from approximately 10 up to 10 000 000 °C/s and more. The combination of various calorimeters and the newly-developed Fast Scanning Calorimeters (FSC) now span 11 orders of magnitude, by which many processes can be mimicked according to the time scale(s) of chemical and physical transitions occurring during cooling, heating and isothermal stays in case heat is exchanged. This not only opens new areas of research on polymers, metals, pharmaceuticals and all kinds of substances with respect to glass transition, crystallization and melting phenomena, it also enables in-depth study of metastability and reorganization of samples on an 1 to 1000 ng scale. In addition, FSC will become a crucial tool for understanding and optimization of processing methods at high speeds like injection molding. The book resembles the state-of-the art in Thermal Analysis & Calorimetry and is an excellent starting point for both experts and newcomers in the field.
| Author | : Ajit S Narang |
| Publisher | : Springer |
| Total Pages | : 700 |
| Release | : 2015-10-07 |
| Genre | : Medical |
| ISBN | : 3319202065 |
In recent years, emerging trends in the design and development of drug products have indicated ever greater need for integrated characterization of excipients and in-depth understanding of their roles in drug delivery applications. This book presents a concise summary of relevant scientific and mechanistic information that can aid the use of excipients in formulation design and drug delivery applications. Each chapter is contributed by chosen experts in their respective fields, which affords truly in-depth perspective into a spectrum of excipient-focused topics. This book captures current subjects of interest – with the most up to date research updates – in the field of pharmaceutical excipients. This includes areas of interest to the biopharmaceutical industry users, students, educators, excipient manufacturers, and regulatory bodies alike.
| Author | : Patrick Augustijns |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 466 |
| Release | : 2007-08-06 |
| Genre | : Medical |
| ISBN | : 0387691545 |
Solvent systems are integral to drug development and pharmaceutical technology. This single topic encompasses numerous allied subjects running the gamut from recrystallization solvents to biorelevant media. The goal of this contribution to the AAPS Biotechnology: Pharmaceutical Aspects series is to generate both a practical handbook as well as a reference allowing the reader to make effective decisions concerning the use of solvents and solvent systems. To this end, the monograph was created by inviting recognized experts from a number of fields to author relevant sections. Specifically, 15 chapters have been designed covering the theoretical background of solubility, the effect of ionic equilibria and pH on solubilization, the use of solvents to effect drug substance crystallization and polymorph selection, the use of solvent systems in high throughput screening and early discovery, solvent use in preformulation, the use of solvents in bio-relevant dissolution and permeation experiments, solvents and their use as toxicology vehicles, solubilizing media and excipients in oral and parenteral formulation development, specialized vehicles for protein formulation and solvent systems for topical and pulmonary drug administration. The chapters are organized such that useful decision trees are included together with the scientific underpinning for their application. In addition, trends in the use of solvent systems and a balance of current views make this monograph useful to both the novice and experienced researcher and to scientists at all developmental stages from early discovery to late pharmaceutical operations.
| Author | : Dennis Douroumis |
| Publisher | : John Wiley & Sons |
| Total Pages | : 404 |
| Release | : 2012-04-24 |
| Genre | : Science |
| ISBN | : 1118307879 |
Hot-melt extrusion (HME) - melting a substance and forcing it through an orifice under controlled conditions to form a new material - is an emerging processing technology in the pharmaceutical industry for the preparation of various dosage forms and drug delivery systems, for example granules and sustained release tablets. Hot-Melt Extrusion: Pharmaceutical Applications covers the main instrumentation, operation principles and theoretical background of HME. It then focuses on HME drug delivery systems, dosage forms and clinical studies (including pharmacokinetics and bioavailability) of HME products. Finally, the book includes some recent and novel HME applications, scale -up considerations and regulatory issues. Topics covered include: principles and die design of single screw extrusion twin screw extrusion techniques and practices in the laboratory and on production scale HME developments for the pharmaceutical industry solubility parameters for prediction of drug/polymer miscibility in HME formulations the influence of plasticizers in HME applications of polymethacrylate polymers in HME HME of ethylcellulose, hypromellose, and polyethylene oxide bioadhesion properties of polymeric films produced by HME taste masking using HME clinical studies, bioavailability and pharmacokinetics of HME products injection moulding and HME processing for pharmaceutical materials laminar dispersive & distributive mixing with dissolution and applications to HME technological considerations related to scale-up of HME processes devices and implant systems by HME an FDA perspective on HME product and process understanding improved process understanding and control of an HME process with near-infrared spectroscopy Hot-Melt Extrusion: Pharmaceutical Applications is an essential multidisciplinary guide to the emerging pharmaceutical uses of this processing technology for researchers in academia and industry working in drug formulation and delivery, pharmaceutical engineering and processing, and polymers and materials science. This is the first book from our brand new series Advances in Pharmaceutical Technology. Find out more about the series here.
