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Title:
The physicochemical basis of pharmaceuticals
Personal Author:
Publication Information:
New York, NY : Oxford University Press, 2009
Physical Description:
xv, 296 p. : ill. (some col.) ; 25 cm.
ISBN:
9780199232840
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30000010226157 RS403 M79 2009 Open Access Book Book
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Summary

Summary

What are the physical and chemical properties that determine how a drug interacts with the body? What determines which dosage form is best, if it will reach its intended target, and how it will be metabolised once it has entered the body?

The Physicochemical Basis of Pharmaceuticals explores the phenomena which affect the formulation and bio-availability of drug substances to give a straightforward, accessible treatment of the essential concepts affecting the absorption and distribution of drugs. It provides the reader with 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.

Focusing at all times on the essential principles and concepts, The Physicochemical Basis of Pharmaceuticals avoids excessive detail, presenting the key facts, backed up with pertinent examples and easy-to-digest illustrations, making it the ideal primer for those who need to understand physicochemical issues in the context of their broader field of study.


Author Notes

Having originally received his BSc and PhD degrees from University College Cork, Humphrey Moynihan returned in 2002, where he is now involved in the teaching of Organic and Pharmaceutical/Medicinal Chemistry. His research interest is the study and control of crystallisation of organic compounds. He is also involved in collaborative research in areas such as Analytical Chemistry.

Abina Crean joined the Cork School of Pharmacy in September 2004 as a Lecturer in Pharmaceutics after working in formulation and process development for Élan Pharmaceutical Technologies and Servier (Ireland) Industries.
Her main research interests are in the areas of solid dose drug delivery systems and pharmaceutical solid-state properties.


Table of Contents

List of Abbreviationsp. xvii
1 Pharmaceuticals and Medicinesp. 1
1.1 Introduction to the essential properties of pharmaceuticalsp. 1
1.1.1 Some key conceptsp. 2
1.2 Classes of pharmaceutical compoundsp. 3
1.2.1 Active pharmaceutical ingredientsp. 4
1.2.2 Excipientsp. 7
1.3 Drug delivery: getting the active pharmaceutical ingredient to the site of actionp. 8
1.3.1 Routes of administrationp. 10
1.3.2 Pharmaceutical dosage formsp. 11
1.3.3 Factors influencing dosage form choicep. 18
1.4 Summaryp. 20
Referencesp. 21
Further Readingp. 21
2 Pharmaceutical Solutionsp. 22
2.1 Definitions and expressions of solubilityp. 22
2.1.1 Measurement of solubility and solubility curvesp. 25
2.2 Solvent structurep. 27
2.2.1 Hydrogen bonding and the structure of waterp. 27
2.2.2 Lipid-based mediap. 29
2.3 Dissolution and solvationp. 31
2.4 Factors affecting solubilityp. 34
2.4.1 Molecular weightp. 34
2.4.2 Hydrogen bondingp. 35
2.4.3 Hydrophobic and hydrophilic groupsp. 36
2.5 Acidity and basicityp. 37
2.5.1 pKa and pKbp. 38
2.5.2 Acidity and environmentp. 42
2.5.3 Buffer solutionsp. 46
2.6 Salt selection and formationp. 48
2.7 Hydrolytic degradationp. 51
2.8 Summaryp. 54
Referencesp. 55
Exercisesp. 55
3 Pharmaceutical Equilibriap. 56
3.1 Essential concepts in thermodynamicsp. 58
3.1.1 Internal energy, enthalpy and the first law of thermodynamicsp. 59
3.1.2 Entropy and the second and third laws of thermodynamicsp. 62
3.1.3 Free energy, chemical potential and equilibriump. 65
3.2 Phase equilibriap. 73
3.2.1 One-component systems and the phase rulep. 74
3.2.2 Two-component systemsp. 78
3.2.3 Three-component systemsp. 84
3.3 Drug delivery: Phase transitionsp. 86
3.3.1 Examples of phase transitions during drug deliveryp. 87
3.3.2 Using phase transitions to understand drug deliveryp. 89
3.3.3 Diffusion (molecular movement within a phase)p. 91
3.3.4 Dissolution (solid-liquid transition)p. 93
3.3.5 Partitioning (liquid-liquid transition)p. 98
3.3.6 Gas absorption (gas-liquid phase transition)p. 100
3.4 Summaryp. 102
Referencesp. 104
Further Readingp. 104
Exercisesp. 104
4 The Pharmaceutical Solid Phasep. 106
4.1 Crystalline and amorphous solidsp. 107
4.2 The essentials of pharmaceutical crystal structurep. 109
4.2.1 Unit cells, crystal systems and latticesp. 109
4.2.2 Space groups and space-group notationp. 112
4.2.3 Crystal planes and facesp. 117
4.3 Crystal polymorphism of pharmaceuticalsp. 118
4.3.1 Relative stabilities of polymorphsp. 120
4.3.2 Solvates and hydratesp. 123
4.4 Methods of characterizing pharmaceutical solidsp. 123
4.4.1 X-ray diffraction methodsp. 124
4.4.2 Thermal methodsp. 129
4.4.3 Other methods of analysisp. 133
4.5 Pharmaceutical crystallizationp. 135
4.5.1 Supersaturationp. 135
4.5.2 Nucleation, growth and crystal morphologyp. 137
4.5.3 Ripening and the rule of stagesp. 138
4.6 Solid-state properties of powder particlesp. 139
4.6.1 Particle shapep. 140
4.6.2 Particle sizep. 141
4.6.3 Particle-size measurementp. 142
4.6.4 Particle surface propertiesp. 144
4.6.5 Moisture adsorptionp. 150
4.6.6 Particle mechanical strengthp. 151
4.7

p. 152

Referencesp. 154
Further Readingp. 154
Exercisesp. 155
5 The Theory of Disperse Systemsp. 156
5.1 Drug distribution in pharmaceutical disperse systemsp. 158
5.2 Molecular, colloidal and coarse disperse systemsp. 159
5.3 The physical stability of disperse systemsp. 162
5.4 Kinetic properties of disperse systemsp. 164
5.4.1 Brownian motionp. 164
5.4.2 Sedimentationp. 165
5.5 Viscosityp. 167
5.5.1 Newtonian and non-Newtonian fluidsp. 169
5.5.2 Colloidal dispersion viscosityp. 172
5.6 Interfacial propertiesp. 174
5.6.1 Interfacial tensionp. 175
5.6.2 Interfacial free energyp. 176
5.6.3 Surfactantsp. 177
5.6.4 Role of interfacial properties in emulsion formationp. 181
5.7 Electrical properties of disperse systemsp. 184
5.7.1 Energies of repulsion and attraction-DLVO theoryp. 187
5.8 Summaryp. 190
Referencesp. 191
Further Readingp. 191
Exercisesp. 191
6 Pharmaceutical Disperse Systemsp. 193
6.1 Pharmaceutical suspensionsp. 193
6.1.1 Factors that influence the stability of pharmaceutical suspensionsp. 195
6.2 Pharmaceutical gelsp. 196
6.2.1 Gel formationp. 197
6.2.2 Drug-loaded gel systemsp. 199
6.2.3 Stability of pharmaceutical gelsp. 200
6.3 Pharmaceutical emulsionsp. 200
6.4 Pharmaceutical microemulsionsp. 202
6.5 Pharmaceutical micellar systemsp. 202
6.6 Pharmaceutical liposomesp. 204
6.7 Pharmaceutical aerosolsp. 208
8.8 Pharmaceutical foamsp. 210
6.9 Summaryp. 210
Further Readingp. 211
7 Drug Partitioning and Transport across Biological Barriersp. 212
7.1 Drug-receptor interactionsp. 213
7.1.1 Types of drug receptorp. 214
7.1.2 Thermodynamics of drug-receptor interactionsp. 215
7.2 Partitioning and partition coefficientsp. 216
7.2.1 Log P valuesp. 217
7.3 Determination of partition coefficientsp. 220
7.3.1 Experimental determination of log Pp. 220
7.3.2 Computational determination of log Pp. 222
7.4 Ionization and distribution coefficientsp. 224
7.4.1 Distribution coefficients of zwitterionic compoundsp. 227
7.5 Cellular and epithelial barriersp. 228
7.5.1 Cellular membrane structurep. 228
7.5.2 Epithelial barriersp. 230
7.6 Transport of drug molecules across cellular barriersp. 232
7.6.1 Paracellular transportp. 232
7.6.2 Transcellular transportp. 233
7.7 Transport of drug molecules in the systemic circulationp. 235
7.7.1 The structure of blood vesselsp. 235
7.7.2 Drug transport across the blood/brain barrierp. 236
7.8 Gastrointestinal drug absorptionp. 237
7.8.1 The small intestinep. 238
7.8.2 The large intestinep. 239
7.8.3 Challenges to drug absorption in the GI tractp. 240
7.9 The skin barrierp. 242
7.9.1 Structure of the skinp. 242
7.9.2 Transport of drug molecules across the skinp. 244
7.10 Other routes of drug administrationp. 245
7.10.1 Drug absorption in the lungsp. 245
7.10.2 Drug absorption in the nasal cavityp. 248
7.10.3 Drug absorption in the oral cavityp. 248
7.11 Summaryp. 250
Referencesp. 252
Further Readingp. 252
Exercisesp. 252
8 Physicochemical Aspects of Pharmacokineticsp. 255
8.1 Absorption, distribution, metabolism and eliminationp. 256
8.2 Bioavailabilityp. 257
8.3 Distributionp. 259
8.4 Drug metabolismp. 263
8.4.1 Phase I metabolismp. 264
8.4.2 Phase II metabolismp. 266
8.5 Excretionp. 269
8.5.1 Excretion processesp. 269
8.5.2 Pharmacokinetic aspects of eliminationp. 271
8.6 Summaryp. 276
Further Readingp. 277
Exercisesp. 277
A.1 Comprehensive List of Routes of Administrationp. 278
A.2 Brief Review of Logarithmsp. 280
A.3 Activities of Ions in Solutionp. 281
A.4 Osmotic Pressurep. 284
A.5 Solutions to æEnd of ChapterÆ Exercisesp. 286
Glossaryp. 288
Indexp. 290
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