The physicochemical basis of pharmaceuticals / Humphrey A. Moynihan, Abina M. Crean.

Format:

Book

Author/Creator:

Moynihan, Humphrey A.

Contributor:

Crean, Abina M.

Language:

English

Subjects (All):

Pharmaceutical chemistry--Textbooks.

Pharmaceutical chemistry.

Chemistry, Pharmaceutical--methods.

Pharmaceutical Preparations--chemistry.

Medical Subjects:

Chemistry, Pharmaceutical--methods.

Pharmaceutical Preparations--chemistry.

Genre:

Textbooks.

Physical Description:

xv, 296 pages : illustrations (some color) ; 25 cm

Place of Publication:

Oxford ; New York : Oxford University Press, 2009.

Summary:

The ideal primer on the physical and chemical basis of drug design and delivery.

Focuses on the essential concepts affecting the absorption and distribution of drugs, with full explanations and extensive worked examples to help you grasps the concepts presented.

Offers broad coverage, but at a depth that's perfect for building a working understanding of the key issues.

Unique insights into dispersal systems and solid state materials-make the book truly rounded in scope.

The Physicochemical Basis of Pharmaceuticals explores the phenomena that affect the design, formulation and bioavailability of drug substances, to give a straightforward introduction to the concepts affecting the absorption and distribution of drugs. It provides the conceptual 'tool-kit' necessary to understand the physicochemical aspects of drug design and action, and shows how these concepts apply in practice.

The book introduces key underlying physical chemistry principles before exploring pharmaceutical solutions, the pharmaceutical solid phase, solid-liquid dispersal systems, biological interfaces, absorption, distribution, metabolism, and excretion, to give a complete view of the field.

The Physicochemical Basis of Pharmaceuticals avoids excessive detail, presenting the key facts, backed up with pertinent examples and easy-to-digest illustrations. It is ideal for any student who needs to understand physicochemical issues in the context of their broader field of study.

Contents:

1 Pharmaceuticals and Medicines 1

1.1 Introduction to the essential properties of pharmaceuticals 1

1.1.1 Some key concepts 2

1.2 Classes of pharmaceutical compounds 3

1.2.1 Active pharmaceutical ingredients 4

1.2.2 Excipients 7

1.3 Drug delivery: getting the active pharmaceutical ingredient to the site of action 8

1.3.1 Routes of administration 10

1.3.2 Pharmaceutical dosage forms 11

1.3.3 Factors influencing dosage form choice 18

1.4 Summary 20

References 21

Further Reading 21

2 Pharmaceutical Solutions 22

2.1 Definitions and expressions of solubility 22

2.1.1 Measurement of solubility and solubility curves 25

2.2 Solvent structure 27

2.2.1 Hydrogen bonding and the structure of water 27

2.2.2 Lipid-based media 29

2.3 Dissolution and solvation 31

2.4 Factors affecting solubility 34

2.4.1 Molecular weight 34

2.4.2 Hydrogen bonding 35

2.4.3 Hydrophobic and hydrophilic groups 36

2.5 Acidity and basicity 37

2.5.1 pKa and pKb 38

2.5.2 Acidity and environment 42

2.5.3 Buffer solutions 46

2.6 Salt selection and formation 48

2.7 Hydrolytic degradation 51

2.8 Summary 54

References 55

Exercises 55

3 Pharmaceutical Equilibria 56

3.1 Essential concepts in thermodynamics 58

3.1.1 Internal energy, enthalpy and the first law of thermodynamics 59

3.1.2 Entropy and the second and third laws of thermodynamics 62

3.1.3 Free energy, chemical potential and equilibrium 65

3.2 Phase equilibria 73

3.2.1 One-component systems and the phase rule 74

3.2.2 Two-component systems 78

3.2.3 Three-component systems 84

3.3 Drug delivery: Phase transitions 86

3.3.1 Examples of phase transitions during drug delivery 87

3.3.2 Using phase transitions to understand drug delivery 89

3.3.3 Diffusion (molecular movement within a phase) 91

3.3.4 Dissolution (solid-liquid transition) 93

3.3.5 Partitioning (liquid-liquid transition) 98

3.3.6 Gas absorption (gas-liquid phase transition) 100

3.4 Summary 102

References 104

Further Reading 104

Exercises 104

4 The Pharmaceutical Solid Phase 106

4.1 Crystalline and amorphous solids 107

4.2 The essentials of pharmaceutical crystal structure 109

4.2.1 Unit cells, crystal systems and lattices 109

4.2.2 Space groups and space-group notation 112

4.2.3 Crystal planes and faces 117

4.3 Crystal polymorphism of pharmaceuticals 118

4.3.1 Relative stabilities of polymorphs 120

4.3.2 Solvates and hydrates 123

4.4 Methods of characterizing pharmaceutical solids 123

4.4.1 X-ray diffraction methods 124

4.4.2 Thermal methods 129

4.4.3 Other methods of analysis 133

4.5 Pharmaceutical crystallization 135

4.5.1 Supersaturation 135

4.5.2 Nucleation, growth and crystal morphology 137

4.5.3 Ripening and the rule of stages 138

4.6 Solid-state properties of powder particles 139

4.6.1 Particle shape 140

4.6.2 Particle size 141

4.6.3 Particle-size measurement 142

4.6.4 Particle surface properties 144

4.6.5 Moisture adsorption 150

4.6.6 Particle mechanical strength 151

4.7 Summary 152

References 154

Further Reading 154

Exercises 155

5 The Theory of Disperse Systems 156

5.1 Drug distribution in pharmaceutical disperse systems 158

5.2 Molecular, colloidal and coarse disperse systems 159

5.3 The physical stability of disperse systems 162

5.4 Kinetic properties of disperse systems 164

5.4.1 Brownian motion 164

5.4.2 Sedimentation 165

5.5 Viscosity 167

5.5.1 Newtonian and non-Newtonian fluids 169

5.5.2 Colloidal dispersion viscosity 172

5.6 Interfacial properties 174

5.6.1 Interfacial tension 175

5.6.2 Interfacial free energy 176

5.6.3 Surfactants 177

5.6.4 Role of interfacial properties in emulsion formation 181

5.7 Electrical properties of disperse systems 184

5.7.1 Energies of repulsion and attraction-DLVO theory 187

5.8 Summary 190

References 191

Further Reading 191

Exercises 191

6 Pharmaceutical Disperse Systems 193

6.1 Pharmaceutical suspensions 193

6.1.1 Factors that influence the stability of pharmaceutical suspensions 195

6.2 Pharmaceutical gels 196

6.2.1 Gel formation 197

6.2.2 Drug-loaded gel systems 199

6.2.3 Stability of pharmaceutical gels 200

6.3 Pharmaceutical emulsions 200

6.4 Pharmaceutical microemulsions 202

6.5 Pharmaceutical micellar systems 202

6.6 Pharmaceutical liposomes 204

6.7 Pharmaceutical aerosols 208

8.8 Pharmaceutical foams 210

6.9 Summary 210

Further Reading 211

7 Drug Partitioning and Transport across Biological Barriers 212

7.1 Drug-receptor interactions 213

7.1.1 Types of drug receptor 214

7.1.2 Thermodynamics of drug-receptor interactions 215

7.2 Partitioning and partition coefficients 216

7.2.1 Log P values 217

7.3 Determination of partition coefficients 220

7.3.1 Experimental determination of log P 220

7.3.2 Computational determination of log P 222

7.4 Ionization and distribution coefficients 224

7.4.1 Distribution coefficients of zwitterionic compounds 227

7.5 Cellular and epithelial barriers 228

7.5.1 Cellular membrane structure 228

7.5.2 Epithelial barriers 230

7.6 Transport of drug molecules across cellular barriers 232

7.6.1 Paracellular transport 232

7.6.2 Transcellular transport 233

7.7 Transport of drug molecules in the systemic circulation 235

7.7.1 The structure of blood vessels 235

7.7.2 Drug transport across the blood/brain barrier 236

7.8 Gastrointestinal drug absorption 237

7.8.1 The small intestine 238

7.8.2 The large intestine 239

7.8.3 Challenges to drug absorption in the GI tract 240

7.9 The skin barrier 242

7.9.1 Structure of the skin 242

7.9.2 Transport of drug molecules across the skin 244

7.10 Other routes of drug administration 245

7.10.1 Drug absorption in the lungs 245

7.10.2 Drug absorption in the nasal cavity 248

7.10.3 Drug absorption in the oral cavity 248

7.11 Summary 250

References 252

Further Reading 252

Exercises 252

8 Physicochemical Aspects of Pharmacokinetics 255

8.1 Absorption, distribution, metabolism and elimination 256

8.2 Bioavailability 257

8.3 Distribution 259

8.4 Drug metabolism 263

8.4.1 Phase I metabolism 264

8.4.2 Phase II metabolism 266

8.5 Excretion 269

8.5.1 Excretion processes 269

8.5.2 Pharmacokinetic aspects of elimination 271

8.6 Summary 276

Further Reading 277

Exercises 277.

Notes:

Includes bibliographical references and index.

ISBN:

9780199232840

0199232849

OCLC:

277068140

Online:

Contributor biographical information

Publisher description