Absorption and drug development : solubility, permeability, and charge state by Avdeef, Alex instant download

Absorption and drug development : solubility, permeability, and charge state by Avdeef, Alex instant download

1 online resource (xxiv, 287 pages) :, Many times drugs work fine when tested outside the body, but when they are tested in the body they fail. One of the major reasons a drug fails is that it cannot be absorb by the body in a way to have the effect it was intended to have. Permeability, Solubility, Dissolution, and Charged State of Ionizable Molecules: Helps drug discovery professionals to eliminate poorly absorbable molecules early in the drug discovery process, which can save drug companies millions of dollars.; Extensive tabulations, in appendix format, of properties and structures of about 200 standard drug molecules, Includes bibliographical references (pages 250-284) and index, Print version record, Cover -- CONTENTS -- PREFACE -- ACKNOWLEDGMENTS -- DEFINITIONS -- 1 INTRODUCTION -- 1.1 Shotgun Searching for Drugs? -- 1.2 Screen for the Target or ADME First? -- 1.3 ADME and Multimechanism Screens -- 1.4 ADME and Medicinal Chemists -- 1.5 The \"A\" in ADME -- 1.6 It is Not Just a Number\"It is a Multimechanism -- 2 TRANSPORT MODEL -- 2.1 Permeability-Solubility-Charge State and the pH Partition Hypothesis -- 2.2 Properties of the Gastrointestinal Tract (GIT) -- 2.3 pH Microclimate -- 2.4 Intracellular pH Environment -- 2.5 Tight-Junction Complex -- 2.6 Structure of Octanol -- 2.7 Biopharmaceutics Classification System -- 3 CHARGE STATE -- 3.1 Constant Ionic Medium Reference State -- 3.2 pK(a) Databases -- 3.3 Potentiometric Measurements -- 3.3.1 Bjerrum Plots -- 3.3.2 pH Definitions and Electrode Standardization -- 3.3.3 The Solubility Problem'' and Cosolvent Methods -- 3.3.4 Use of Cosolvents for Water-Soluble Molecules -- 3.4 Spectrophotometric Measurements -- 3.5 Capillary Electrophoresis Measurements -- 3.6 Chromatographic pK(a) Measurement -- 3.7 pK(a) Microconstants -- 3.8 pK(a) \"Gold Standard\" for Drug Molecules -- 4 PARTITIONING INTO OCTANOL -- 4.1 Tetrad of Equilibria -- 4.2 Conditional Constants -- 4.3 log P Databases -- 4.4 log D -- 4.5…