Physicochemical Principles of Pharmacy: In Manufacture, Formulation and Clinical Use

664 Pages·2015·147.069 MB·English

by  Alexander T. Florence, David Attwood

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Physicochemical Principles of Pharmacy
In Manufacture, Formulation and Clinical Use

Physicochemical Principles
of Pharmacy
In Manufacture, Formulation and
Clinical Use
SIXTH EDITION
Alexander T Florence CBE, DSc, FRSE, FRSC, FRPharmS
UCL School of Pharmacy, University College London, UK
David Attwood PhD, DSc, CChem, FRSC
Manchester Pharmacy School
University of Manchester, UK
Published byPharmaceutical Press
66–68 EastSmithfield,London E1W1AW
©RoyalPharmaceuticalSociety 2016
isa trade markofPharmaceuticalPress
PharmaceuticalPressis thepublishing divisionofthe
RoyalPharmaceutical Society
First,secondandthirdeditionspublished by
Palgrave(formerlyMacmillan PressLtd)1981, 1988,1998
Thirdedition reprinted2004, 2005
Fourthedition 2006
Fourthedition reprinted 2007,2009
Fifth edition 2011
Sixthedition 2016
TypesetbyData StandardsLtd,Frome,Somerset, UK
Printedin Great BritainbyTJ International, Padstow,Cornwall
ISBN:978 0857111746 (print)
ISBN:978 0857112583 (ePDF)
ISBN:978 0857112590 (ePub)
ISBN:978 0857112606 (mobi)
Allrightsreserved. Nopartofthispublication may bereproduced,
storedin aretrievalsystem,or transmittedin anyformorbyanymeans,
without theprior writtenpermission ofthe copyright holder.
The publisher makesnorepresentation, expressorimplied,withregard
totheaccuracyoftheinformationcontainedin thisbookandcannot accept
anylegalresponsibilityorliabilityforanyerrorsoromissionsthatmaybemade.
The rightsofAlexander TFlorenceandDavidAttwoodtobeidentified
astheauthorsofthisworkhavebeen asserted bythem inaccordancewiththe
Copyright, Designs andPatentsAct,1988.
Acatalogue recordfor thisbookis availablefromtheBritish Library.
To our wives
Florence and Renee
for their long-standing patience and understanding.

Contents
Preface xiii
About the authors xv
Introduction 1
1 Solids 7
1.1 Classification of solids 8
1.2 Crystalline solids: structure and properties 8
1.3 Amorphous solids 25
1.4 Dissolution of solid drugs 25
1.5 Biopharmaceutical importance of particle size 26
1.6 Wetting of powders 29
1.7 Freeze drying 32
1.8 Solid-dosage forms: formulation and manufacture 34
1.9 Solid dispersions 63
Summary 66
References 68
2 Physicochemical properties of drugs in solution 69
2.1 Concentration units 69
2.2 Thermodynamics: a brief introduction 71
2.3 Activity and chemical potential 75
2.4 Osmotic properties of drug solutions 80
2.5 Ionisation of drugs in solution 87
2.6 Diffusion of drugs in solution 105
Summary 106
References 107
3 Drug stability 109
3.1 The chemical decomposition of drugs 109
3.2 Kinetics of chemical decomposition in solution 118
3.3 Solid-dosage forms: kinetics of chemical decomposition 127
3.4 Factors influencing drug stability 129
3.5 Stability testing and prediction of shelf-life 141
Summary 149
References 150
viii | Contents
4 The solubility of drugs 153
4.1 Definitions 154
4.2 Factors influencing solubility 154
4.3 Measurement of solubility 169
4.4 The solubility parameter 170
4.5 Solubility in mixed solvents: use of cosolvents 171
4.6 Cyclodextrins as solubilising agents 174
4.7 Solubility problems in formulation 177
4.8 Partitioning 181
4.9 Biological activity and partition coefficients: thermodynamic activity and Ferguson’s principle 183
4.10 Using log P 183
Summary 190
References 191
5 Surfactants 193
5.1 Amphipathic compounds 194
5.2 Surface and interfacial properties of surfactants 195
5.3 Micellisation 218
5.4 Liquid crystals and surfactant vesicles 227
5.5 Properties of some commonly used surfactants 231
5.6 Solubilisation 237
Summary 244
References 244
6 Emulsions, suspensions and related colloidal systems 247
6.1 Colloids and their classification 248
6.2 Colloid stability 249
6.3 Disperse system flow 255
6.4 Emulsions 261
6.5 Suspensions 279
6.6 Miscellaneous colloidal systems 288
6.7 Applications of colloid stability theory to other systems 288
6.8 Foams 291
Summary 293
References 294
7 Polymers and macromolecules 295
7.1 Pharmaceutical polymers 296
7.2 Water-soluble polymers 301
7.3 General properties of polymer solutions 302
7.4 Water-soluble polymers used in pharmacy and medicine 311
7.5 Water-insoluble polymers and polymer membranes 323
7.6 Some applications of polymeric systems in drug delivery 331
Summary 349
References 349
Further reading 350
Contents | ix
8 Drug absorption basics and the oral route 351
8.1 Biological membranes and drug transport 352
8.2 The oral route and oral absorption 360
8.3 Oral dosage forms 365
8.4 Buccal and sublingual absorption 371
Summary 374
References 375
Further reading 375
9 Parenteral routes of drug administration 377
9.1 Intravenous and intra-arterial administration 378
9.2 Intramuscular and subcutaneous injection 379
9.3 Transdermal delivery 386
9.4 Topical treatment of the nails: transungual therapy 397
9.5 Medication of the eye and the eye as a route for systemic delivery 398
9.6 The ear (the aural route) 406
9.7 Absorption from the vagina 407
9.8 Inhalation therapy 408
9.9 The nasal route 417
9.10 Rectal absorption of drugs 419
9.11 Drug administration to brain, spinal cord and tissues 422
Summary 425
References 426
10 Paediatric and geriatric formulations 427
10.1 Introduction 427
10.2 Paediatric medication 428
10.3 The elderly and their medication 437
Summary 440
References 440
11 Physicochemical interactions and incompatibilities 443
11.1 pH effects in vitro and in vivo 444
11.2 Dilution of mixed-solvent systems 450
11.3 Cation–anion interactions 451
11.4 Polyions and drug solutions 454
11.5 Chelation 454
11.6 Other complexes 458
11.7 Adsorption of drugs 464
11.8 Drug interactions with plastics 466
11.9 Protein binding 467
11.10 Reflections on interactions 472
Summary 475
Appendix: Drug interactions based on physical mechanisms 476
References 478
Further reading 479