Absorption and Drug Development - Solubility, Permeability, and Charge State

Informationen zum Autor ALEX AVDEEF , PhD, is the founder of in-ADME Research. He has more than thirty years of experience in chemical instrumentation and software development. Internationally recognized as an authority in the field of solution chemistry, Dr. Avdeef has an extensive list of scholarly publications to his credit. Klappentext Explains how to perform and analyze the results of the latest physicochemical methodsWith this book as their guide, readers have access to all the current information needed to thoroughly investigate and accurately determine a compound's pharmaceutical properties and their effects on drug absorption. The book emphasizes oral absorption, explaining all the physicochemical methods used today to analyze drug candidates. Moreover, the author provides expert guidance to help readers analyze the results of their studies in order to select the most promising drug candidates.This Second Edition has been thoroughly updated and revised, incorporating all the latest research findings, methods, and resources, including:* Descriptions and applications of new PAMPA models, drawing on more than thirty papers published by the author's research group* Two new chapters examining permeability and Caco-2/MDCK and permeability and the blood-brain barrier* Expanded information and methods to support pKa determination* New examples explaining the treatment of practically insoluble test compounds* Additional case studies demonstrating the use of the latest physicochemical techniques* New, revised, and expanded database tables throughout the bookWell over 200 drawings help readers better understand difficult concepts and provide a visual guide to complex procedures. In addition, over 800 references serve as a gateway to the primary literature in the field, facilitating further research into all the topics covered in the book.This Second Edition is recommended as a reference for researchers in pharmaceutical R&D as well as in agrochemical, environmental, and other related areas of research. It is also recommended as a supplemental text for graduate courses in pharmaceutics. Zusammenfassung Explains how to perform and analyze the results of the latest physicochemical methods With this book as their guide, readers have access to all the current information needed to thoroughly investigate and accurately determine a compound's pharmaceutical properties and their effects on drug absorption. Inhaltsverzeichnis Preface xxiii Preface to the First Edition xxvii List of Abbreviations xxxi Nomenclature xxxv Commercial Trademarks xli 1 Introduction 1 1.1 Bulldozer Searching for a Needle in the Haystack? 1 1.2 As the Paradigm Turns 4 1.3 Screen for the Target or ADME First? 5 1.4 ADME and Multimechanism Screens 6 1.5 ADME and the Medicinal Chemist 7 1.6 The "Absorption" in ADME 8 1.7 It Is Not Just a Number It Is a Multimechanism 9 References 9 2 Transport Model 12 2.1 Permeability-Solubility-Charge State and pH-Partition Hypothesis 12 2.2 Properties of the Gastrointestinal Tract (GIT) 17 2.3 pH Microclimate 22 2.4 Intracellular pH Environment 23 2.5 Tight Junction Complex 23 2.6 Structure of Octanol 23 2.7 Biopharmaceutics Classification System 25 References 26 3 pKa Determination 31 3.1 Charge State and the pKa 32 3.2 Methods of Choice for the Determination of the pKa 34 3.3 Titration with a Glass-Membrane pH Electrode 34 3.4 Equilibrium Equations and the Ionization Constant 38 3.5 "Pure Solvent" Activity Scale 41 3.6 Ionic Strength and Debye-Hückel/Davies Equation 41 3.7 "Constant Ionic Medium" Activity Scale 43 3.8 Temperature Dependence of pKa Values 47 3.9 Electrode Calibration and Standardization 55 3.1...

Product details

• Authors: Avdeef, A Avdeef, Alex Avdeef, Alex (Pion Avdeef, Avdeef Alex
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 08.06.2012
• EAN: 9781118057452
• ISBN: 978-1-118-05745-2
• No. of pages: 744
• Subject: Natural sciences, medicine, IT, technology > Chemistry > Miscellaneous