Advanced Formulation and Processing Technologies in the Oral Delivery of Poorly Water-soluble Drugs
Advanced Formulation and Processing Technologies in the Oral Delivery of Poorly Water-soluble Drugs

Author: Bo Lang

Publisher:

Published: 2013

Total Pages: 726

ISBN-13:

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With the advance of combinational chemistry and high throughput screening, an increasing number of pharmacologically active compounds have been discovered and developed. A significant proportion of those drug candidates are poorly water-soluble, thereby exhibiting limited absorption profiles after oral administration. Therefore, advanced formulation and processing technologies are demanded in order to overcome the biopharmaceutical limits of poorly water-soluble drugs. A number of pharmaceutical technologies have been investigated to address the solubility issue, such as particle size reduction, salt formation, lipid-based formulation, and solubilization. Within the scope of this dissertation, two of the pharmaceutical technologies were investigated names thin film freezing and hot-melt extrusion. The overall goal of the research was to improve the oral bioavailability of poorly water-soluble drugs by producing amorphous solid dispersion systems with enhanced wetting, dissolution, and supersaturation properties. In Chapter 1, the pharmaceutical applications of hot-melt extrusion technology was reviewed. The formulation and process development of hot-melt extrusion was discussed. In Chapter 2, we investigated the use of thin film freezing technology combined with template emulsion system to improve the dissolution and wetting properties of itraconazole (ITZ). The effects of formulation variables (i.e., the selection of polymeric excipients and surfactants) and process variables (i.e., template emulsion system versus cosolvent system) were studied. The physic-chemical properties and dissolution properties of thin film freezing compositions were characterized extensively. In Chapter 3 and Chapter 4, we investigated hot-melt extrusion technology for producing amorphous solid dispersion systems and improving the dissolution and absorption of ITZ. Formulation variables (i.e., the selection of hydrophilic additives, the selection of polymeric carriers) and process variables (i.e., the screw configuration of hot-melt extrusion systems) were investigated in order to optimize the performance of ITZ amorphous solid dispersions. The effects of formulation and process variables on the properties of hot-melt extrusion compositions were investigated. In vivo studies revealed that the oral administration of advanced ITZ amorphous solid dispersion formulations rendered enhanced oral bioavailability of the drug in the rat model. Results indicated that novel formulation and processing technologies are viable approaches for enhancing the oral absorption of poorly water-soluble drugs.

Formulating Poorly Water Soluble Drugs
Formulating Poorly Water Soluble Drugs

Author: Robert O. Williams III

Publisher: Springer

Published: 2016-12-16

Total Pages: 781

ISBN-13: 3319426095

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The objective of this volume is to consolidate within a single text the most current knowledge, practical methods, and regulatory considerations pertaining to formulations development with poorly water-soluble molecules. A pharmaceutical scientist’s approach toward solubility enhancement of a poorly water-soluble molecule typically includes detailed characterization of the compound’s physiochemical properties, solid-state modifications, advanced formulation design, non-conventional process technologies, advanced analytical characterization, and specialized product performance analysis techniques. The scientist must also be aware of the unique regulatory considerations pertaining to the non-conventional approaches often utilized for poorly water-soluble drugs. One faced with the challenge of developing a drug product from a poorly soluble compound must possess at minimum a working knowledge of each of the abovementioned facets and detailed knowledge of most. In light of the magnitude of the growing solubility problem to drug development, this is a significant burden especially when considering that knowledge in most of these areas is relatively new and continues to develop

Formulating Poorly Water Soluble Drugs
Formulating Poorly Water Soluble Drugs

Author: Robert O. Williams III

Publisher: Springer Science & Business Media

Published: 2011-12-04

Total Pages: 656

ISBN-13: 1461411440

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This volume is intended to provide the reader with a breadth of understanding regarding the many challenges faced with the formulation of poorly water-soluble drugs as well as in-depth knowledge in the critical areas of development with these compounds. Further, this book is designed to provide practical guidance for overcoming formulation challenges toward the end goal of improving drug therapies with poorly water-soluble drugs. Enhancing solubility via formulation intervention is a unique opportunity in which formulation scientists can enable drug therapies by creating viable medicines from seemingly undeliverable molecules. With the ever increasing number of poorly water-soluble compounds entering development, the role of the formulation scientist is growing in importance. Also, knowledge of the advanced analytical, formulation, and process technologies as well as specific regulatory considerations related to the formulation of these compounds is increasing in value. Ideally, this book will serve as a useful tool in the education of current and future generations of scientists, and in this context contribute toward providing patients with new and better medicines.

Drug Delivery Strategies for Poorly Water-Soluble Drugs
Drug Delivery Strategies for Poorly Water-Soluble Drugs

Author: Dionysios Douroumis

Publisher: John Wiley & Sons

Published: 2012-12-19

Total Pages: 543

ISBN-13: 1118444671

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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.

Enhancing Delivery of Poorly Water-soluble Drugs by Innovative Amorphous Solid Dispersions
Enhancing Delivery of Poorly Water-soluble Drugs by Innovative Amorphous Solid Dispersions

Author: Scott Victor Jermain

Publisher:

Published: 2019

Total Pages: 0

ISBN-13:

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Poorly water-soluble drugs continue to dominate today’s drug development pipelines, and thus a multitude of technologies and solubility-enhancing methodologies have been commercialized to address this issue. One-such methodology to enhance the solubility of poorly water-soluble drugs is the development of amorphous solid dispersions. What was once considered a risky method of drug delivery (due to lack of drug kinetic stability in its amorphous state), formulating drugs as amorphous solid dispersions has grown significantly over the past two decades. Two amorphous solid dispersion-producing technologies have become well-understood for the development and successful delivery of poorly water-soluble drugs, and thus an overwhelming majority of commercialized amorphous solid dispersion products are processed by these two technologies; hot melt extrusion and spray drying. Each technology has distinct advantages and disadvantages, and thus many poorly water-soluble drugs are unable to process by either technology using conventional techniques. Thus, novel utilization of excipients and processing methods is necessary to continually expand the formulation design space. Furthermore, the development and commercialization of novel amorphous solid dispersion-producing technologies is necessary to further-expand the formulation design space. Therefore, the following research is an effort to expand the formulation design space of poorly water-soluble drugs while forming amorphous solid dispersions. The following research focuses on continued innovation in the field of amorphous solid dispersions to enhance the bioavailability of poorly water-soluble drugs. These research directions demonstrate innovative use of an ordinary excipient to enhance delivery of amorphous solid dispersions processed by hot melt extrusion. Additionally, these studies demonstrate the use (and further understanding) of a novel technology, KinetiSol, that allows for processing amorphous solid dispersions without the necessity of external thermal input or solvent(s). KinetiSol-processed materials are compared with spray dried materials to evaluate the kinetics behind drug release of a weakly basic drug processed with an ionic polymer, and findings from this study will be essential for future delivery of amorphous solid dispersions of weakly basic drugs in ionic polymers

Oral Lipid-Based Formulations
Oral Lipid-Based Formulations

Author: David J. Hauss

Publisher: CRC Press

Published: 2007-06-08

Total Pages: 370

ISBN-13: 1420017268

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Oral lipid-based formulations are attracting considerable attention due to their capacity to facilitate gastrointestinal absorption and reduce or eliminate the effect of food on the absorption of poorly water-soluble, lipophilic drugs. Despite the obvious and demonstrated utility of these formulations for addressing a persistent and growing problem

Developing Solid Oral Dosage Forms
Developing Solid Oral Dosage Forms

Author: Yihong Qiu

Publisher: Academic Press

Published: 2016-11-08

Total Pages: 1178

ISBN-13: 0128026375

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Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice, Second Edition illustrates how to develop high-quality, safe, and effective pharmaceutical products by discussing the latest techniques, tools, and scientific advances in preformulation investigation, formulation, process design, characterization, scale-up, and production operations. This book covers the essential principles of physical pharmacy, biopharmaceutics, and industrial pharmacy, and their application to the research and development process of oral dosage forms. Chapters have been added, combined, deleted, and completely revised as necessary to produce a comprehensive, well-organized, valuable reference for industry professionals and academics engaged in all aspects of the development process. New and important topics include spray drying, amorphous solid dispersion using hot-melt extrusion, modeling and simulation, bioequivalence of complex modified-released dosage forms, biowaivers, and much more. Written and edited by an international team of leading experts with experience and knowledge across industry, academia, and regulatory settings Includes new chapters covering the pharmaceutical applications of surface phenomenon, predictive biopharmaceutics and pharmacokinetics, the development of formulations for drug discovery support, and much more Presents new case studies throughout, and a section completely devoted to regulatory aspects, including global product regulation and international perspectives

Nanoparticle Formulations of Poorly Water Soluble Drugs and Their Action in Vivo and in Vitro
Nanoparticle Formulations of Poorly Water Soluble Drugs and Their Action in Vivo and in Vitro

Author: Troy Powell Purvis

Publisher:

Published: 2007

Total Pages: 530

ISBN-13:

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Poorly water soluble drugs have been manipulated to make them more soluble, increasing the bioavailability of these drugs. Several cryogenic processes allow for production of drug nanoparticles, without mechanical stress that could cause degradation. The Ultra Rapid Freezing (URF) process is a technique which improves water solubility of drugs by reducing primary drug particle size by producing amorphous solid dispersions. Heat conduction is improved, using a cryogenic material with a high thermal conductivity relative to the solution being frozen to maintain the surface temperature and heat transfer rate while the solution is being frozen. With URF technology, the freezing rate is fixed, which drives the particle formation and determines its characteristics. Supersaturation of drug in aqueous solution can allow for better absorption of the drug via the oral and pulmonary routes. Drug formulations that supersaturate the dissolution media show the possibility for increased bioavailability from an amorphous drug form. If the concentration of drug in solution is significantly increased, higher chemical potential will lead to an increase in flux across an exposed membrane, leading to higher blood levels for an amorphous drug, compared to an identical crystalline formulation. During oral delivery, supersaturated drug concentrations would also saturate PGP efflux sites in the gut lumen, increasing the drug's bioavailability. Saturated PGP sites show zero order efflux kinetics, so increasing the drug concentration in supersaturated biological fluid will increase serum drug levels. High supersaturation levels maintained for prolonged periods would have a beneficial effect on a drug's absolute bioavailability. Pulmonary administration offers therapeutic advantages over more invasive routes of administration. Limited amount of metabolizing enzymes like CYP 3A4 in lung tissue along with avoidance of first pass metabolism are advantages to pulmonary delivery. The objective of the research presented in this dissertation is to show the versatility of nanoparticulate poorly water soluble drug formulations. Due to the reduced particle size and the URF manufacturing process, a wide range of applications can be used with these nanoparticles. Oral and pulmonary administration routes can be explored using nanoparticles, but in vitro cell culture testing can show clinical benefits from this type of processing technology.

Water-Insoluble Drug Formulation
Water-Insoluble Drug Formulation

Author: Ron Liu

Publisher: CRC Press

Published: 2008-01-18

Total Pages: 686

ISBN-13: 1420009559

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Scientists have attributed more than 40 percent of the failures in new drug development to poor biopharmaceutical properties, particularly water insolubility. Issues surrounding water insolubility can postpone, or completely derail, important new drug development. Even much-needed reformulation of currently marketed products can be significantly affected by these challenges. Water Insolubility is the Primary Culprit in over 40% of New Drug Development Failures The most comprehensive resource on the topic, this second edition of Water Insoluble Drug Formulation brings together a distinguished team of experts to provide the scientific background and step-by-step guidance needed to deal with solubility issues in drug development. Twenty-three chapters systematically describe solubility properties and their impact on formulation, from theory to industrial practice. With detailed discussion on how these properties contribute to solubilization and dissolution, the text also features six brand new chapters on water-insoluble drugs, exploring regulatory aspects, pharmacokinetic behavior, early phase formulation strategies, lipid based systems for oral delivery, modified release of insoluble drugs, and scalable manufacturing aspects. The book includes more than 15 water-insoluble drug delivery systems or technologies, illustrated with case studies featuring oral and parenteral applications. Highlighting the most current information and data available, this seminal volume reflects the significant progress that has been made in nearly all aspects of this field.

Multiparticulate Drug Delivery
Multiparticulate Drug Delivery

Author: Ali R. Rajabi-Siahboomi

Publisher: Springer

Published: 2017-05-26

Total Pages: 402

ISBN-13: 1493970127

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Authored by leading experts from academia, users and manufacturers, this book provides an authoritative account of the science and technology involved in multiparticulate drug delivery systems which offer superior clinical and technical advantages over many other specialized approaches in drug delivery. The book will cover market trends, potential benefits and formulation challenges for various types of multiparticulate systems. Drug solubility, dose, chemistry and therapeutic indications as well as excipient suitability coupled with manufacturing methods will be fully covered. Key approaches for taste-masking, delayed release and extended release of multiparticulates systems are of significant interest, especially their in-vivo and in-vitro performance. In addition, the principles of scale-up, QbD, and regulatory aspects of common materials used in this technology will be explained, as well as recent advances in materials and equipment enabling robust, flexible and cost-effective manufacture. Case studies illustrating best practices will also make the book a valuable resource to pharmaceutical scientists in industry and academia.