Computer-Aided Drug Design and Delivery Systems Book

Preface

1 Computer-Aided Drug Design (CARD) 1

1.1 Introduction 1

1.2 Rational Drug Design 1

1.3 Factors Contributing to Drug Discovery 3

1.4 Drug Design with the Help of Software 3

1.5 Drug Discovery Process 3

1.6 How Computers Help in Drug Design 4

1.7 Computer Simulation for Drug Design 6

1.8 Drug Design Theory 6

1.9 Role of Computers in Drug Design: Their Success and Failure 9

1.10 Rational Drug Design Software 10

1.10.1 Scanners 10

1.10.2 Builders 12

1.10.3 Hybrids 13

1.11 RACHEL Software Package 13

1.11.1 RACHEL Component Specification Language 14

References 16

2 Drug Delivery Systems 17

2.1 Introduction 17

2.2 Development of Sustained-Release Drug Delivery Systems 18

2.2.1 Delayed-Release Systems 19

2.2.2 Advantages of Sustained Drug Delivery Systems 20

2.3 Important Physicochemical Properties of the Drug 20

2.3.1 Aqueous Solubility and pK, 20

2.3.2 Partition Coefficient 20

2.3.3 Drug Stability 21

2.3.4 Protein Binding 21

2.4 Biologic Properties 21

2.4.1 Absorption 21

2.4.2 Distribution 21

2.4.3 Metabolism 22

2.4.4 Elimination and Biologic Half-Life 22

2.5 Safety Considerations 22

2.6 Transdermal Delivery Systems 22

2.6.1 Membrane-Moderated Systems 23

2.6.2 Adhesive Diffusion-Controlled Systems 23

2.6.3 Matrix Dispersion-Type Systems 23

2.6.4 Microreservoir Systems 24

2.7 Targeted Delivery Systems 24

2.7.1 Nanoparticles 24

2.7.2 Liposomes 24

2.7.3 Resealed Erythrocytes 25

2.8 Transdermal Delivery Systems 26

2.9 Basic Components of Transdermal Devices 27

2.10 Choice of Drug 28

2.11 Excipients 29

2.12 Adhesive and Packaging 29

2.13 Pressure-Sensitive Adhesives 30

2.13.1 Peel Adhesion Properties 30

2.13.2 Tack Properties 30

2.13.3 Shear Strength Properties 31

2.14 Transdermal Devices 31

2.14.1 Membrane-Moderated Devices (Reservoir Devices) 31

2.14.2 Adhesive Diffusion-Type Devices (Mixed Monolithic Reservoir Devices) 33

2.14.3 Matrix Dispersion-ControlledDevice (Monolithic Device) 33

2.14.4 Microreservoir-Type Devices 34

2.14.5 Microreservoir Dissolution-Controlled Devices 35

2.15 In Vitro Release Kinetics 35

2.16 In Vitro Skin-Permeation Kinetics 36

2.17 IV-IV Correlation 36

2.18 Optimization of Transdermal Systems 36

2.19 Skin Irritation Sensitization 37

References 37

3 Bioinformatics of Drug Molecules and Databases 39

3.1 Introduction 39

3.2 The Concepts, Goals, and Aims of Bioinformatics 40

3.3 Fields of Bioinformatics: Role and Relevance in Biotechnology 40

3.4 Proteomics: Protein Sequence Databases 42

3.5 Data Retrieval Systems 43

3.6 System Retrieval Systems 43

3.7 Applications of Bioinformatics 44

3.8 Bioinformatics in Rational Drug Design and the Medical Sciences 44

3.9 Bioinformatics and Chemical Engineering 47

3.10 Brief Introduction to Bioinformatics Databases 48

3.11 Microarray Database 51

3.12 Bioinformatics Scenario 52

References 54

4 Lipase- and Esterase-Mediated Drugs and Drug Intermediates 57

4.1 Introduction 57

4.2 Lipase Used in Biotransformations 57

4.2.1 Solvents for Biocatalysis 58

4.2.2 Sources of Lipase 58

4.2.3 Location of Action 59

4.2.4 Structure of Lipase 59

4.2.5 Mechanism of Action 59

4.2.6 Production of Lipase 60

4.2.7 Statistical Design Approach for Optimization of Process Parameters and Nutritional Requirement for Lipase Production 61

4.2.8 Immobilization 61

4.2.9 Role of Lipases in the Preparation of Drugs and Drug Intermediates 63

4.3 Esterase as Hydrolase Enzyme 77

4.3.1 Esterase Production 77

4.3.2 Preparation of Drugs and Drug Intermediates by Esterases 79

References 87

5 Pharmacokinetics and Pharmacodynamics in Drugs 91

5.1 Introduction 91

5.2 Pharmacokinetic Parameters 91

5.3 Pharmacodynamic Parameters 92

5.4 Absorption of Drugs 93

5.4.1 Factors Affecting Drug Absorption 93

5.4.2 Mechanism of Drug Absorption 93

5.4.3 Factors Influencing Drug Absorption 97

5.4.4 Manufacturing Variables 103

5.5 Distribution of Drugs 104

5.5.1 Factors Affecting Drug Distribution 104

5.5.2 Factors Affecting Differences in the Distribution of Drugs 104

5.5.3 Plasma Protein Binding 105

5.5.4 Physiologic Barriers 106

5.6 Biotransformation/Metabolism 108

5.7 Excretion of Drugs 124

5.7.1 Pharmacokinetic Equations 126

5.8 Pharmacodynamics 128

5.8.1 Factors Influencing Drug Action 130

5.8.2 How Does a Drug Act? 132

References 135

6 Biomarkers, Biosensors, and Robotics in Medicine 137

6.1 Introduction 137

6.2 Developmental History of Biomarkers 138

6.3 Different Types of Biomarkers 139

6.4 Use of Biomarkers in Cancer 143

6.5 Biomarkers in Medical Science 146

6.6 Recent Advances in Biomarkers 146

6.7 Disadvantages of Biomarkers 147

6.8 Biosensors 147

6.9 Developmental History of Biosensors 148

6.10 General Instrumentation and Operation of a Biosensor 149

6.11 Biosensors in Drug Design 152

6.12 Biosensors in Biomedical Research 152

6.13 Robotics in Surgery 157

6.14 Background and History of Surgical Robots 158

6.15 Robot-Assisted Surgery 160

6.16 Advantages and Disadvantages of Robot-Assisted Surgery 163

6.17 Applications of Robotic Surgery 164

6.18 Practical Uses of Surgical Robots Today 165

6.19 Future of Robotic Surgery 165

6.20 Conclusion 166

References 167

7 Biomedical Instrumentation 169

7.1 Introduction 169

7.2 Biomedical Instrumentation Measurements 170

7.2.1 Instrumentation for Cardiovascular Measurements 172

7.3 Measurement of Blood Flow and Cardiac Output 178

7.3.1 Measurement of Heart Sounds 181

7.3.2 Instrumentation for Measurements of the Nervous System 181

7.3.3 Electromyographic Measurements 183

7.4 Instrumentation for Psychophysiologic Measurements 184

7.5 Instrumentation for the Experimental Analysis of Behavior 185

7.6 Respiratory Therapy Equipment 186

7.7 Pacemakers and Defibrillators 186

7.8 Instrumentation for the Medical Use of Radioisotopes 188

7.9 Ophthalmic and ENT Instruments 188

7.10 Ultrasonography 192

7.11 Computed Tomographic Scanning (CT Scanning) 195

7.12 Positron-Emission Tomographic (PET) Scanning 196

7.13 Magnetic Resonance Imaging 197

References 198

Index 201