Download or read book The Production and Stabilization of Pharmaceutical Nanosuspensions written by Francis S. Romanski and published by . This book was released on 2011 with total page 259 pages. Available in PDF, EPUB and Kindle. Book excerpt: The production and stabilization of pharmaceutical nanosuspensions has been a recent focus of the pharmaceutical industry where it has been shown that nanosuspensions of poorly water-soluble drugs exhibit a greatly increased dissolution rate, and as a consequence, an increased in vivo bioavailability. Accordingly, the ability to manufacture stable pharmaceutical nanosuspensions in a fast, safe, and predictable manner would be highly advantageous. However, the small size is not without consequence; the prodigious amount of available surface area in combination with van der Waals forces quickly cause irreversible agglomeration, destroying the desired properties, and thus requiring the use of surfactants for any combination of steric, electrostatic, and kinetic stabilization. As a result, this work focused on two distinct methods for producing pharmaceutical nanosuspensions, as well as the important role that surfactants play in stabilization. In the first method, high pressure homogenization was used to mill suspensions by forcing them through a minute piston gap, where particles were subjected to a combination of shear, cavitation, and grinding. This technique was optimized for use by incorporating excipients for novel formulations in situ with the goal of producing capsules, films, and oral-suspensions. Alternatively, the shortcomings present in all accepted nano-sizing methodologies led to the development of the emulsion precipitation method. In this process, nanoparticles as small as 60 nm were produced by extracting drug nanoparticles from an O/W emulsion made from partially miscible components. It was found that formulations utilizing any one of five contrastive solvents could be used to create nanosuspensions based not on intrinsic drug properties, but rather on droplet size, solvent diffusion, and surfactant choice, rendering this technique arguably the most robust currently available. Finally, the recurrent issue of stability was addressed through a series of molecular dynamics simulations and corresponding experiments to elucidate the molecular phenomena present at the surfaces of nano-scale crystals. Several case studies measured the interfacial binding energy between a surfactant and a crystal surface, where strong interactions were indicative of a longer shelf-life, quenched growth rates, and predictable crystal morphologies. It is hoped, that the culmination of this work will greatly advance our ability to produce, stabilize, and deliver poorly-soluble drugs.

Download or read book Production and Stabilization of Nanosuspensions of Poorly Soluble Drug Substances written by Ana Maria Mendes Cerdeira and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs written by Rainer H. Müller and published by CRC Press. This book was released on 1998 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: Explore possible new approaches for overcoming poorly soluble drugs - a challenge to drug formulation work and an increasing problem. Many newly developed drugs are poorly soluble, very often simultaneously in aqueous and in organic media. Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs aims to: review the possibilities, limitations and future perspectives of emulsions as drug carriers considering technology from other than the phamaceutical industry (i.e food industry). show the production technology of nanosuspensions, explain the special dissolution properties (i.e. increased saturation solubility) and increased dissolution velocity (theory), and cover the possible applications. present the theory of high pressure homogenization and high pressure extrusion in dispersion techniques, including examples of applications and size measurements in concentrated dispersions.

Download or read book Early Drug Development 2 Volume Set written by Fabrizio Giordanetto and published by John Wiley & Sons. This book was released on 2018-12-10 with total page 810 pages. Available in PDF, EPUB and Kindle. Book excerpt: This one-stop reference systematically covers key aspects in early drug development that are directly relevant to the discovery phase and are required for first-in-human studies. Its broad scope brings together critical knowledge from many disciplines, ranging from process technology to pharmacology to intellectual property issues. After introducing the overall early development workflow, the critical steps of early drug development are described in a sequential and enabling order: the availability of the drug substance and that of the drug product, the prediction of pharmacokinetics and -dynamics, as well as that of drug safety. The final section focuses on intellectual property aspects during early clinical development. The emphasis throughout is on recent case studies to exemplify salient points, resulting in an abundance of practice-oriented information that is usually not available from other sources. Aimed at medicinal chemists in industry as well as academia, this invaluable reference enables readers to understand and navigate the challenges in developing clinical candidate molecules that can be successfully used in phase one clinical trials.

Download or read book Batch and Continuous Production of Stable Dense Suspensions of Drug Nanoparticles in a Wet Stirred Media Mill written by Afolawemi Afolabi and published by . This book was released on 2013 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: One way to improve the bioavailability of poorly water-soluble drugs is to reduce particle size of drug crystals down to nanoscale via wet stirred media milling. An increase in total surface area per mass loading of the drug and specific surface area as well as reduced external mass transfer resistance allow a faster dissolution of the poorly-water soluble drug from nanocrystals. To prevent aggregation of nanoparticles, polymers and surfactants are dissolved in water acting as stabilizers via adsorption onto the drug crystals. In the last two decades, ample experimental data were generated in the area of wet stirred media milling for the production of drug nanoparticle suspensions. However, a fundamental scientific/engineering understanding of various aspects of this process is still lacking. These challenges include elucidation of the governing mechanism(s) during nanoparticle formation and physical stabilization of the nanosuspension with the use of polymers and surfactants (formulation parameters), understanding the impact of process parameters in the context of first-principle-based models, and production of truly nanosized drug particles (10-100 nm) with acceptable physical stability and minimal contamination with the media. Recirculation mode of milling operation, where the drug suspension in a holding tank continuously circulates through the stirred media mill, has been commonly used in lab, pilot, and commercial scales. Although the recirculation is continuous, the recirculation operation mode is overall a batch operation, requiring significant number of batches for a large-volume pharmaceutical product. Hence, development and investigation of a truly continuous process should offer significant advantages. To explain the impact of some of the processing parameters, stress intensity and stress number concepts were widely used in literature, which do not account for the effect of suspension viscosity explicitly. The impact of the processing parameters has not been explained in a predictive and reliable manner. In this dissertation, a comprehensive investigation of the production of Griseofulvin nanosuspensions in a wet stirred media mill operating in both the recirculation and continuous modes has been conducted to address the aforementioned fundamental challenges. Griseofulvin has been selected as a model poorly water-soluble BCS Class II drug. Impact of various formulation parameters such as stabilizer type and loading as well as processing parameters such as rotor speed, bead loading, bead size, suspension flow rate and drug loading was studied. A major novelty of the present contribution is that the impact of processing and formulation parameters has been analyzed and interpreted using a combined experimental-theoretical (microhydrodynamic model) approach. Such a comprehensive approach allowed us to intensify the process for the production of sub-100 nm drug particles, which could not be produced with top-down approaches in the literature so far. In addition, a multi-pass mode of continuous operation was developed and the so-called "Rehbinder effect", which has not been shown for the breakage of drug particles, was also elucidated. The dissertation work (1) indicated the need for a minimum polymeric stabilizer-to-drug ratio for proper stabilization of drug nanosuspensions as dictated by polymer adsorption and synergistic interactions between a polymeric stabilizer and a surfactant, (2) demonstrated the existence of an optimum polymer concentration from a breakage rate perspective in the presence of a surfactant, which results from the competing effects of viscous dampening and enhanced steric stabilization at higher polymer concentration, (3) developed fundamental understanding of the breakage dynamics-processing-formulation relationships and rationalized preparation of a single highly drug-loaded batch (20% or higher) instead of multiple dilute batches, (4) designed an intensified process for faster preparation of sub-100 nm particles with reduced specific energy consumption and media wear (i.e. minimal drug contamination), and (5) provided first evidence for the proof of Rehbinder effect during the milling of drugs. Not only do the polymers and surfactants allow proper physical stabilization of the nanoparticles in the suspensions, but they also do facilitate drug particle breakage. This dissertation also discusses applications of nanosuspensions and practical issues encountered during wet media milling.

Download or read book Pharmaceutical Suspensions written by Alok K. Kulshreshtha and published by Springer Science & Business Media. This book was released on 2009-11-05 with total page 337 pages. Available in PDF, EPUB and Kindle. Book excerpt: The suspension dosage form has long been used for poorly soluble active ingre- ents for various therapeutic indications. Development of stable suspensions over the shelf life of the drug product continues to be a challenge on many fronts. A good understanding of the fundamentals of disperse systems is essential in the development of a suitable pharmaceutical suspension. The development of a s- pension dosage form follows a very complicated path. The selection of the proper excipients (surfactants, viscosity imparting agents etc.) is important. The particle size distribution in the finished drug product dosage form is a critical parameter that significantly impacts the bioavailability and pharmacokinetics of the product. Appropriate analytical methodologies and instruments (chromatographs, visco- ters, particle size analyzers, etc.) must be utilized to properly characterize the s- pension formulation. The development process continues with a successful scale-up of the manufacturing process. Regulatory agencies around the world require cli- cal trials to establish the safety and efficacy of the drug product. All of this devel- ment work should culminate into a regulatory filing in accordance with the regulatory guidelines. Pharmaceutical Suspensions, From Formulation Development to Manufacturing, in its organization, follows the development approach used widely in the pharmaceutical industry. The primary focus of this book is on the classical disperse system – poorly soluble active pharmaceutical ingredients s- pended in a suitable vehicle.

Download or read book Encyclopedia of Colloid and Interface Science written by Tharwat Tadros and published by Springer. This book was released on 2013-06-28 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: An authoritative and comprehensive reference relevant to all scientists and engineers in the field. This encyclopedia not only helps chemistry, materials science and physics researchers to understand the principles, but also provides practicing engineers with the necessary information for implementing practical applications, such as Food and agrochemicals Polymers and ceramics Cosmetics and detergents Paints and coatings Pharmaceuticals and drug delivery In addition, the encyclopedia is an important reference for industrial chemists and chemical engineers faced with a multitude of industrial systems of a colloidal nature. As wide as the range of applications that colloid and interface science has is the range of scientific disciplines that contribute to research and development in this field. These encompass chemistry, physics, biology and mathematics as well as nanoscience and nanotechnology. The encyclopedia provides easy-to-digest information for meeting these interdisciplinary challenges. While providing numerous concise definitions of key terms, the encyclopedia also features more than forty in-depth essays on topics ranging from Agrochemical Formulations to Zeta Potential. All entries are cross-referenced and include selected references to original literature as well as synonyms.

Download or read book Innovative Dosage Forms written by Yogeshwar Bachhav and published by John Wiley & Sons. This book was released on 2019-12-04 with total page 470 pages. Available in PDF, EPUB and Kindle. Book excerpt: Teaches future and current drug developers the latest innovations in drug formulation design and optimization This highly accessible, practice-oriented book examines current approaches in the development of drug formulations for preclinical and clinical studies, including the use of functional excipients to enhance solubility and stability. It covers oral, intravenous, topical, and parenteral administration routes. The book also discusses safety aspects of drugs and excipients, as well as regulatory issues relevant to formulation. Innovative Dosage Forms: Design and Development at Early Stage starts with a look at the impact of the polymorphic form of drugs on the preformulation and formulation development. It then offers readers reliable strategies for the formulation development of poorly soluble drugs. The book also studies the role of reactive impurities from the excipients on the formulation shelf life; preclinical formulation assessment of new chemical entities; and regulatory aspects for formulation design. Other chapters cover innovative formulations for special indications, including oncology injectables, delayed release and depot formulations; accessing pharmacokinetics of various dosage forms; physical characterization techniques to assess amorphous nature; novel formulations for protein oral dosage; and more. -Provides information that is essential for the drug development effort -Presents the latest advances in the field and describes in detail innovative formulations, such as nanosuspensions, micelles, and cocrystals -Describes current approaches in early pre-formulation to achieve the best in vivo results -Addresses regulatory and safety aspects, which are key considerations for pharmaceutical companies -Includes case studies from recent drug development programs to illustrate the practical challenges of preformulation design Innovative Dosage Forms: Design and Development at Early Stage provides valuable benefits to interdisciplinary drug discovery teams working in industry and academia and will appeal to medicinal chemists, pharmaceutical chemists, and pharmacologists.

Download or read book Interfacial Forces in Aqueous Media written by Carel J. van Oss and published by CRC Press. This book was released on 2006-05-22 with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly revised and reorganized, the second edition of Interfacial Forces in Aqueous Media examines the role of polar interfacial and noncovalent interactions among biological and nonbiological macromolecules as well as biopolymers, particles, surfaces, cells, and both polar and apolar polymers. The book encompasses Lifshitz-van de

Download or read book Pharmaceutical Crystals written by Tong Li and published by John Wiley & Sons. This book was released on 2018-10-16 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: An important resource that puts the focus on understanding and handling of organic crystals in drug development Since a majority of pharmaceutical solid-state materials are organic crystals, their handling and processing are critical aspects of drug development. Pharmaceutical Crystals: Science and Engineering offers an introduction to and thorough coverage of organic crystals, and explores the essential role they play in drug development and manufacturing. Written contributions from leading researchers and practitioners in the field, this vital resource provides the fundamental knowledge and explains the connection between pharmaceutically relevant properties and the structure of a crystal. Comprehensive in scope, the text covers a range of topics including: crystallization, molecular interactions, polymorphism, analytical methods, processing, and chemical stability. The authors clearly show how to find solutions for pharmaceutical form selection and crystallization processes. Designed to be an accessible guide, this book represents a valuable resource for improving the drug development process of small drug molecules. This important text: Includes the most important aspects of solid-state organic chemistry and its role in drug development Offers solutions for pharmaceutical form selection and crystallization processes Contains a balance between the scientific fundamental and pharmaceutical applications Presents coverage of crystallography, molecular interactions, polymorphism, analytical methods, processing, and chemical stability Written for both practicing pharmaceutical scientists, engineers, and senior undergraduate and graduate students studying pharmaceutical solid-state materials, Pharmaceutical Crystals: Science and Engineering is a reference and textbook for understanding, producing, analyzing, and designing organic crystals which is an imperative skill to master for anyone working in the field.

Download or read book Handbook of Stability Testing in Pharmaceutical Development written by Kim Huynh-Ba and published by Springer Science & Business Media. This book was released on 2008-11-16 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: This handbook is the first to cover all aspects of stability testing in pharmaceutical development. Written by a group of international experts, the book presents a scientific understanding of regulations and balances methodologies and best practices.

Download or read book Nanodispersions written by Tharwat F. Tadros and published by Walter de Gruyter GmbH & Co KG. This book was released on 2015-12-14 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: General introduction - Definition of nanodispersions (nanosuspensions, nanoemulsions, swollen micelles or microemulsions, liposomes and vesicles) and their size range. General description of their colloid stability. Main advantages of nanodispersions and their industrial applications. Preparation of nanosuspensions by top-up process - Nucleation and growth and control of particle size distribution. Factors determining the formation of narrow particle size distribution. Role of surfactants and polymers. Preparation of nano-polymer colloids (lattices) by emulsion and dispersion polymerization. Factors affects the stability of nanosuspensions. Preparation of nanosuspensions by bottom down process - Dispersion of preformed particles in liquids and the need of a wetting agent. Break-up of aggregates and agglomerates by application of high speed stirrers. Reduction of particle size by application of intense energy (microfluidization or bead milling). Maintenance of the colloid stability of the resulting particles. Reduction of Ostwald ripening. Industrial applications of nanosuspensions - Application in pharmacy to enhance bioavailability, Application in sunscreens for UV protection. Application in paints and coatings. Preparation of nanoemulsions by the use of high pressure homogenisers - Principles of emulsion formation and the role of the emulsifier. Selection of emulsifiers. Methods of emulsification and prevention of coalescence during emulsification. Origin of colloid stability of nanoemulsions. Prevention of Ostwald ripening Low energy methods for nanoemulsion preparation - The phase inversion composition method and the role of mixing the surfactant with oil and water. The phase inversion temperature method for preparation of nanoemulsions. Preparation of nanoemulsions by dilution of microemulsions. Practical examples of nanoemulsions and their industrial application - Nanoemulsions based on non-ionic surfactants and the role of the hydrophilic-lipophilic balance. Effect of oil solubility on the stabilityof nanoemulsions. Nanoemulsions based on polymeric surfactants. Applications in pharmacy and cosmetics. Swollen micelles or microemulsionsDefinition of microemulsions and their size range. Thermodynamic definition of microemulstions. Theories of microemulsion formation and stability. Characterisation of microemulsions using scattering, conductivity and NMR rechniques. Formulation of microemulsions and their industrial applications - Distinction between microemulsions and macroemulsions. Formulation of oil/water and water/oil microemulsions. Selection of emulsifiers for microemulsions. Application of microemulsions in tertiary oil recovery. Liposomes and vesicles - Formation of multilamellar lipid layers (liposomes) by dispersion of lipids in water. Formation of unilamellar vesicles by sonication of the liposomes. Factors responsible for stabilisation of liposomes and vesicles. Use of block copolymers to enhance the stability of vesicles. Applications of liposomes and vesicles in pharmacy and cosmetics.

Download or read book Drug Delivery Strategies for Poorly Water Soluble Drugs written by Dionysios Douroumis and published by John Wiley & Sons. This book was released on 2012-12-19 with total page 543 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many newly proposed drugs suffer from poor water solubility, thus presenting major hurdles in the design of suitable formulations for administration to patients. Consequently, the development of techniques and materials to overcome these hurdles is a major area of research in pharmaceutical companies. Drug Delivery Strategies for Poorly Water-Soluble Drugs provides a comprehensive overview of currently used formulation strategies for hydrophobic drugs, including liposome formulation, cyclodextrin drug carriers, solid lipid nanoparticles, polymeric drug encapsulation delivery systems, self–microemulsifying drug delivery systems, nanocrystals, hydrosol colloidal dispersions, microemulsions, solid dispersions, cosolvent use, dendrimers, polymer- drug conjugates, polymeric micelles, and mesoporous silica nanoparticles. For each approach the book discusses the main instrumentation, operation principles and theoretical background, with a focus on critical formulation features and clinical studies. Finally, the book includes some recent and novel applications, scale-up considerations and regulatory issues. Drug Delivery Strategies for Poorly Water-Soluble Drugs is an essential multidisciplinary guide to this important area of drug formulation for researchers in industry and academia working in drug delivery, polymers and biomaterials.

Download or read book Nanoparticulate Drug Delivery written by Vandana Patravale and published by Elsevier. This book was released on 2012-10-31 with total page 244 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanotechnology-based therapeutics, operating at scales of billionths of a metre, have great potential for future expansion in altering the scale and methods of drug delivery. The availability of these novel formulations to once-inaccessible areas of the body has greatly expanded the therapeutic window of existing drug molecules. Nanoparticulate drug delivery highlights and examines the transition of nanoparticulate drug delivery systems from the laboratory into a commercially viable sector. The first chapters of the book provide an overview of the use and characterization of nanoparticulate systems as drug carriers, including the assessment of their morphology, sterility and potential toxicity. In the latter part of the book, chapters cover nanotoxicology, regulatory aspect and clinical trials, ending with an overview of several case studies and a look towards future developments. - Discusses the issues surrounding nanoparticulate products, based on personal experience of their formulation - Provides an overview of new application areas, including RNA interference - Outlines the pros and cons of nanoparticulate products, and discusses how these may influence their route into the commercial sector

Download or read book Handbook of Pharmaceutical Controlled Release Technology written by Donald L. Wise and published by CRC Press. This book was released on 2000-08-24 with total page 908 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Handbook of Pharmaceutical Controlled Release Technology reviews the design, fabrication, methodology, administration, and classifications of various drug delivery systems, including matrices, and membrane controlled reservoir, bioerodible, and pendant chain systems. Contains cutting-edge research on the controlled delivery of biomolecules! Discussing the advantages and limitations of controlled release systems, the Handbook of Pharmaceutical Controlled Release Technology covers oral, transdermal, parenteral, and implantable delivery of drugs discusses modification methods to achieve desired release kinetics highlights constraints of system design for practical clinical application analyzes diffusion equations and mathematical modeling considers environmental acceptance and tissue compatibility of biopolymeric systems for biologically active agents evaluates polymers as drug delivery carriers describes peptide, protein, micro-, and nanoparticulate release systems examines the cost, comfort, disease control, side effects, and patient compliance of numerous delivery systems and devices and more!

Download or read book Modified release Drug Delivery Technology written by and published by . This book was released on 2008 with total page 696 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Lipid Nanoparticles Production Characterization and Stability written by Rohan Shah and published by Springer. This book was released on 2014-08-28 with total page 105 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​What are lipid nanoparticles? How are they structured? How are they formed? What techniques are best to characterize them? How great is their potential as drug delivery systems? These questions and more are answered in this comprehensive and highly readable work on lipid nanoparticles. This work sets out to provide the reader with a clear and understandable understanding of the current practices in formulation, characterization and drug delivery of lipid nanoparticles. A comprehensive description of the current understanding of synthesis, characterization, stability optimization and drug incorporation of solid lipid nanoparticles is provided. Nanoparticles have attracted great interest over the past few decades with almost exponential growth in their research and application. Their small particle size and subsequent high surface area make them ideal in many uses, but particularly as drug carrier systems. Nanoparticles made from lipids are especially attractive because of their enhanced biocompatibility imparted by the lipid. The work provides a detailed description of the types of lipid nanoparticles available (e.g. SLN, NLC, LDC, PLN) and how they range from imperfect crystalline to amorphous in structure. Current thoughts on where drugs are situated (e.g. in the core, or at the interface) and how this can be manipulated are discussed. The many techniques for production, including the author’s own variant of microwave heating, are fully discussed. Techniques for measuring arguably the most important characteristics of particle size and polydispersity are discussed, along with techniques to measure crystallinity, shape and drug capacity. Finally, a full chapter on techniques for measuring stability, both in the absence and presence of drugs, is discussed, along with suggestions on how to optimize that stability. This work appeals to students of colloid science, practitioners of research into drug delivery and academics alike.