Index

a-helix 497 absorption 372 et seq

of acidic and basic drugs 378, 379 and antacids 454 buccal 392-395 from emulsions 280 from the eye 418 from the ear 425 from the gastrointestinal tract 379,

386 et seq from inclusion complexes 470 from injections 395 et seq intranasal 437 et seq log P and 376 percutaneous 408 rectal 441 et seq vaginal 426 et seq

absorption bases 408 acacia see gum arabic acetanilide, solubility of 157 acetylsalicylic acid

absorption of 378, 379 adsorption on to charcoal 223 binding of 4 72 decomposition in solid state 121, 137, 138 decomposition in suppositories 137 and gastric bleeding 26 hydrolysis in suspensions Ill ionisation 80, 81 transacetylation 137

achlorhydria 453 acicular crystals 8 acid

conjugate 81 defined 81 polyprotic 88-90 weak, dissociation of 81, 82

acid-base pairs 81 acid-base catalysis I 02, 124-129 acidic drugs

absorption of 190, 192, 378, 379 (table), 380 ionisation of 80 et seq, 378-380 partitioning of 183-185 pH of 90 et seq solubility of 163-165

acidity constant 82 AcrH 438 activated charcoal 219, 223, 473 activation energy 130, 140, 143 activity (thermodynamic)

and biological activity 187 defined 63 of ionised drugs 64-67 mean ionic 65 and osmotic pressure 73 of solvents 67-69 in topical preparations 409, 410

activity coefficient 64-67, 409 adhesion 294, 296, 342, 343, 540 et seq adhesional wetting 296 adhesives, pressure-sensitive 353 (table) adhesivity

of dosage forms 540-543 measurement of 541-543

adipic acid II adjuvants 2 adrenaline 423 adsorbents 221 et seq

adsorption of amphoteric compounds 221 by antacids 222, 223 of drugs 216-218, 472-475 factors affecting 220 et seq of insulin 329-331 isotherms 216 et seq, 520 ofmacromolecules 328-331 medical and pharmaceutical applications of

222, 223 by microbial cells 300 physical and chemical 216 on plastics 223, 224, 347-348 of preservatives 194 of proteins and peptides 475, 506, 507 at solid/liquid interface 220 et seq of toxins 222, 223 of water by proteins 519, 520

aerodynamic diameter 441 Aerosil 295, 443 aerosols 36, 254, 543 et seq

deposition 429, 430 et seq, 436 delivered dose 549 generation of 435-437 propellants 38-40, 434

alburrrin 478,479,482,483 alginates 336, 337 Aludrox 222 aluminium hydroxide gel 222, 474 alveolar concentrations of gases 52 alveoli 429 Amberlite 351 amide hydrolysis 102 amino acids

hydrophobicity 500 structures 494, 495

aminobenzoic acid decomposition of 122, 123 microdissociation constants 191 partitioning of 188, 190, 191

aminophylline suppositories 534 aminosalicylic acid, decomposition of

120, 122, 136 amphipathic molecules see surfactants amphipathy 199 amphiphiles see surfactants amphiprotic solvents 82 amphoteric drugs 122, 166 amphoteric electrolytes 88 ampicillin polymerisation 108, 109, 114 anaesthetic gases 38, 43, 44

partition coefficients 49, 77 (table) solubility in blood and tissues 51 et seq

anaesthetics, local adsorption of 219, 220, 224 surface activity 207

anioncation interactions 459-461 anionic surfactants 200, 238 antacids

and absorption 454, 455 adsorption on 222, 223 and gastric emptying 454 and gastric pH 452 neutralising capacity of 453 (table)

antibiotics 483 antidepressants

adsorption of 218 surface actiivity of 218

552 Index

antihistamines membrane interaction of 214 surface activity of 206, 207

antioxidants 105, 134, 514 anus 442 APAP excretion 445 aqueous humour 419 Arrhenius equation 130, 131, 139, 140, 515, 516 aspirin see acetylsalicylic acid association colloids 225 atactic copolymers 310, 311 attapulgite 473 Autohaler 435 autoxidation I 03 p-azoxyanisole 235

,8-blockers corneal permeability of 421, 422 log P values 421 (table)

,8-elimination 514 ,8-sheet 498 baclofen 446 bacteria

growth of 67 sorption of 300, 30 I

bactericidal concentrations and activity 187 (table) barbiturates

adsorption of 223 polymorphism of 14 solubilisation of 245 (table)

barium sulphate 291 base

conjugate 81 defined 81 polyprotic 88-90 weak, dissociation of 82

base-catalysis 102, 124-129 basic drugs

absorption of 192, 378, 379 (table), 380 ionisation of 80 et seq partitioning of 185 pH of 91 et seq solubility of 164-166

basicity constant 83 batch control 527 et seq beclomethasone dipropionate 438

solvates of 18 Becodisk 438 bentonite 221, 289, 474, 475 benzalkonium chloride 239 benzanilide, eutectic mixtures of 33 benzethonium chloride 297 benzoic acid 184, 248, 475 betamethasone 407, 408 bicontinuous phases 234, 275 bile salts 387, 389, 390 binding

ions to macromolecules 325 of proteins 477 et seq

bioadhesion 342, 343 bioadhesive devices 392 bioavailability

of drugs applied to the eye 418 from eutectic mixtures 32 from intramuscular injections 395 et seq particle size and 23 of phenobarbitone 23 polymorphic forms and 16 from rectal formulations 441 from subcutaneous injections 395 et seq

biological activity and log P 186 et seq, 376 and particle size 23 and solubility 181 and thermodynamic activity 187

biological membranes 373 et seq composition of 373-375 flnid mosaic model 3 7 5 and insoluble films 214, 215 lipophilic character 3 77 permeability of 421 pH at surface of 381 solute transport in 375, 376 structure of 3 7 5 surface charge of 376

biopharmaceutics, emulsions 278 biophase model of 195 bishydroxycoumarin see dicoumarol bismuth compounds 289 block copolymers 309, 321, 322 blood

buffer capacity of 96 colloidal properties of 302 et seq flow of 398, 457 pH of 81 solubility of gases in 50 et seq viscosity 302

body fluids, pH 81 (table) Bohr effect 50 boiling point

of alcohols 155 elevation of 45, 46 and solubility 155

Born forces 256 bovine somatotropin 519 BP impinger apparatus 547-549 Bravais lattice 6, 7 bridging 292 BmnstedBjerrum equation 132 Bmnsted catalysis law 127 buccal absorption 392, 393, 394 buffer 93 et seq

capacity 94-96 and drug stability 124-127 preparation of 93 universal 96

Bufferin 455 bulk laxatives 328 Bunsen's absorption coefficient 46 buserilin 415 Butazolidin-Alka 455

Caco-2 cells 517 caffeine 468-470 caking of suspensions 286, 287, 289 calcitonin 524 calcium

binding of 325, 464 (table) solubility 451

calcium glubionate 75, 76 carbomer see Carbopol carbon black, adsorption on 216-218 carbon haemoperfusion 223 Carbopol 332, 333, 343, 428 carboxymethylcellulose 26, 289, 334 carboxypolymethylene see Carbopol catalysis, acidbase 102, 124-129 Catapress TIS 368 cationanion interactions 459-461 cationic surfactants 200 cavitation 415 Celevac 330 ,!1-cell, artificial 402 cell membrane models 214 cellcell interactions 299 cellulose acetate phthalate 213 cellulose derivatives 332 et seq cephaloridine, solvates of 18 cephalosporin esters 90, 106, 483, 484 cerebrospinal fluid (CSF) 446

cetomacrogol 1000 241 cetrimide 239 (table) CFC propellants 38 charcoal, activated 223, 473 charge transfer interactions 469 chelation 453, 463 et seq chemical decomposition 101 et seq, 471 chemical potential 69 et seq

of component in solution 71 defined 69 of electrolytes 72 of non-electrolytes 71 of two-phase systems 71, 187

chemisorption 216 chloramphenicol 32, 297 chloramphenicol palmitate 17,

polymorphism of 17 chlordiazepoxide degradation 119 chlorofluorocarbons 38, 39, 434 chloroform 48 chlorothiazide 471 chlorpromazine

affinity for plastics 347, 348 partition coefficient 385 photochemical decomposition of 107, 108 surface activity of 207

cholesteric liquid crystals 235 cholesterol

and biological membranes 375 monolayers 210, 215

cholestyramine 351, 471, 472 (tables) chondroitin 324 chylomicrons 281 ciclosidomine 124, 130, 131 cimetidine 453 cinchocaine 102 ciprofloxacin, absorption 466 cis-trans isomerisation 107 ClausiusClapeyron equation 41 et seq clays, adsorption by 222 clobetasol propionate, solubility 412 (table) cloud point

-y~rystallin 503 of nonionic surfactant& 232

erne see critical micelle concentration coacervation 358, 359 (table), 360 cocoa butter 441, 442 codeine sulphate degradation 125-127, 130 cohesive energy density 173 colestipol 471 colligative properties 72 colloids

classification of 254, 255 forces of interaction 256 et seq stability of 255 et seq, 298 et seq

common ion effect 180 complex reactions 115-120 complexation 323 et seq, 463 et seq, 469 et seq concentration units 56-58 condensed monolayers 209 conjugate acid 81 consecutive reactions 119 conservation of energy 58 consistency 537, 539 contact angle

and chemical structure 28 of pharmaceutical powders 29 (table) and wettability 27

contact lenses 321, 423-425 continuous phase 252 contraceptive ring 428 contrast media 193, 291, 459 controlled flocculation 286-292 controlled release devices 354 et seq convective flow 381

copolymers 309, 310 copperglycine chelate 463 cornea 416, 417 cortexolone 407 cortexone 407

Index 553

cosolvent systems 174, 175, 457, 458, 459 in protein formulations 507

cosurfactant 274 Coulter counter method (dissolution testing) 528 coumarins, chelation 465, 466 counterions

binding to micelle 229 effect on erne 231

Cremophor EL 241 critical surface tension, cornea 417 critical micelle concentration 205, 224

factors affecting 230 et seq of polysorbates 240 (table)

-y-crystallin, cloud point of solutions 503 crystals

dissolution 153 form 8 growth 10 habits 8 hydrates 18 polymorphs II et seq lattice 5 Miller indices 7 structure 5

crystallinity of polymers 344, 345 crystallisation 9 CSF 446 cubic phase 234, 322 cyclizine 206 cyclodextrins 174-177,470, 471 cyclosporin 276

De-Nol 289 Debrisan 343 Debye-Hiickel theory 66 decomposition (chemical) 102 et seq

of acetylsalicylic acid 137, 138 of aminobenzoic acid 123 of aminosalicylic acid 120, 122, 136 of ampicillin 109 of cephalosporin esters 106 of chlordiazepoxide 119 of chlorpromazine 107, 108 of ciclosidamine 124, 131 of codeine sulphate 125-127, 130 factors affecting 123 et seq of indomethacin 138 kinetics of I 09 et seq of mecillinam 128, 129 of morphine I 04 of nitrazepam 117 of oils and fats I 03 of paracetamol 137 of penicillin G 135 of phentolamine 132, 133 of pilocarpine 106 of proteins 504, 509 et seq of riboflavine 143, 144 in semisolid dosage forms 135 in solid dosage forms 120 et seq, 135 et seq,

146 of somatotropin 520 in suspensions 145 of tetracyclines 105 of vitamin A 107 of vitamin E succinate 139

deflocculation 286-292 denaturation, proteins 496, 502, 504, 505 dendrimers 311, 312 Deponit 368, 369, 370

554 Index

deposition see aerosol deposition desferrioxamine 469 desmopressin 440 dexamethasone

elixir 75 intravenous preparation of 75 polymorphism 15, 16

dextran 314, 337-339, 397, crosslinked 343

dextranomer 343 dextrose infusions, pH 168, 450 (table) diazepam injection, i.m. 399 dichlorodifluoromethane 39 dichlorotetrafluoroethane 39 dicoumarol (bishydroxycoumarin) 25, 465, 466 dielectric constant 134, 174, 257, 503 diffusion

of aerosol particles 432 and crystallisation I 0 and dissolution 21 of drugs in solution 96 et seq Fick's laws of 97, 98 in hydrogels 326 in intrathecal drug administration 447 in matrices 357 in polymers 344, 345, 346 (table) of proteins 516, 517 in skin 404, 405, 410 et seq Stokes-Einstein equation 98

diffusion coefficients of drugs 99 (table) of proteins 517 (table)

digoxin adsorption 222, 474 amorphous 17 bioavailability 26, 473 elixir 75, 76 intravenous preparations 75 polymorphism 15

dilution of mixed solvent systems 457 of topical preparations 135

dimethicones 305, 352 dimethyluracil 470 diodoquin, zinc chelate 467 diphenhydramine 206, 207 diphenylmethane drugs, micellar properties

231 (table) dipivoyl adrenaline (dipivoyl epinephrine) 423 disodium cromoglycate 428, 429, 433, 435, 459, 460 disorder and entropy 60 disperse phase 252 dispersions 252 et seq dissociation constants

of water 85 (table) of weak acids and bases 82, 83

see also microdissociation constants dissolution 21 et seq

and crystal form 20 of eutectic mixtures 31 and particle size 25 parameters affecting 22

dissolution tests flow-through method 530-531, 532 pharmacopoeial methods 528-530 solid dose forms 527 et seq of suppository formulations 532, 534 of transdermal systems 533, 535-7

distribution coefficients see partition coefficients disulphide formation, proteins 514 DLVO theory 256 et seq dodecyl methylbetaine 199 dodecyltrimethylammonium bromide, erne

232 (table) donoracceptor complexes 469

dosage forms adhesivity 540 et seq dissolution testing of 527 et seq

double layer 229, 257, 258 doxycycline 188 drug release 326, 327, 355, 363 drugs

absorption of 372 et seq adsorption of 216-220, 223 chemical stability of 102 et seq diffusion of 96 et seq distribution into human milk 196 (table) incompatibilities of 449 et seq, 485 et seq (table) interactions of 449 et seq, 476-478,

485 et seq (table) ionisation of 80 et seq log P values 189 (table) micellisation of 231 microdissociation constants 88-90 osmotic properties of 72 et seq physicochemical properties of 56 et seq pK. values 83-85 protein binding of 477 et seq salts 80, 82, 92

choice of 179-181 pH of 92, 93 solubility of 179 (table}, 180 (table) see also electrolytes

solubility of !52 et seq sorption into PVC 195 (table) surface activity of 206-208, 214

drug-infant formula mixtures 76 duodenum 81, 387, 388

ear 425 effective concentration 63 Einstein viscosity equation 317 electrical double layer 229, 257, 258 electrolytes

activity of 64 amphoteric 88 and drug stability 132 chemical potential of 72 and colloid stability 259, 260 effect on drug solutions 461, 462 and HLB 270, 271 and micellar properties 232 osmolality of 73 and protein solubility 503 solubility of 161

electro-osmosis 414 electrostatic forces (in colloidal dispersions) 257 electroviscous effect 294 Emla 32 Emulsifying Wax 238 emulsions 252 et seq, 264 et seq

absorption from 280 biopharmaceutics of 278 HLB system and 266-270 intravenous fat 281-283 mass transport in 280-281 microbial spoilage of 279, 280 microemulsions 272-276 multiple 270-272 partitioning in 279, 280 photomicrographs of 253 pourability of 283 preservatives, availability in 279, 280 rheology of 283-285 self-bodied 277, 278 semisolid 277, 278 spreadability 283 stability 264-266 structured 277, 278 viscosity of 283-285

endothermic processes 58 energy (thermodynamics) 58, 59 enflurane 40, 53, 77 enoxacin 467 enthalpic stabilisation 260, 261 enthalpy

of binding of drugs 481 and colloid stability 260-263 defined 59 affusion 46 of micellisation 225 of solution 47, 161 of vaporisation 41-43

entropy of binding of drugs 481 and colloid stability 260-262 and disorder 60 of micellisation 225

environmental factors and stability 147 ephedrine derivatives, percutaneous 412 epimerisation see isomerisation epinephrine 423 4-epi-tetracycline 105 epithelium, small intestine 387 equilibrium constant 62, 63 equivalents 57 ergotamine 468 eroding systems 364, 365 erythrocytes 338, 483 erythromycin salts 180 (table) Escherichia coli 301, 302 ester hydrolysis I 0 I Estraderm 368 ethylcellulose 332 ethylhydroxycellulose 334 ethylmethylcellulose 334 eucalyptol 41 Eudragits 354 eutectic mixtures 30, 31

and dissolution rate 31 and drug identification 32 formulation containing 32

eutectic point 30 eutectic temperatures of drugs

33 (table) excipients 2

and stability 136 Exorbin 351 exothermic processes 58 extensive properties 69 eye

absorption from 418 medication of 416 et seq ointment 419 structure of 416

eye drops formulation of 419 et seq systemic effects 425

faeces, pH of 81 fats

absorption pathways 390 emulsions 281 oxidation of 103

Ferguson's principle 186 fibrinogen 479 Pick's laws

and diffusion of drugs 96-98 and diffusion in skin 403 and permeability of polymers 345

film coating materials 213, 354, 542, 544 first law of thermodynamics 59 first-order reactions 111, 112 flavours, partitioning of 280

flocculation controlled 286-292 and deflocculation 286, 287 and zeta potential 288

flocculating agents 291 Flory temperature 327

Index 555

flow-through dissolution systems 530-531, 532 fludrocortisone solvates 18 fluid mosaic model, membranes 375 fluocinonide, release from cream 535 fluoromethalone 420 fluoromethane 44 foams 304-306 forces

Born 256 electrostatic 256 van der Waals 227, 256

formaldehyde, polymerisation of 109 formulation

of acidbase mixtures 177-179 adsorption problems in 223, 224 choice of drug salt 179-181 depot medication 356 of eye drops 419 et seq of insulin 400-403 of intramuscular injections 397, 398 of microemulsions 274, 276 of proteins 507 et seq, 516 et seq of self-bodied emulsions 277-278 of suppositories 443-446 of suspensions 291 of topicals 408

Frandol 368 Franklin, Benjamin 208 free energy 61 et seq

of binding 481 defined 61 of dilution 327 of hydration 19 of micellisation 225, 227 of partitioning 185 of polymeric forms 17 of reactions 62 surface 200

freezing point depression 45, 46, 79 Freundlich equation 218-220 frictional ratio, proteins 517 (table) froth test 306

gadobenic acid 468 gadolinium-BOPTA chelate 469 GALT 23,386 gamma scintigraphy 434 gas constant 36 gas laws 36-38 gaseous monolayers 210 gases 36 et seq

anaesthetic 49, 51-54, 76 ideal and nonideal 36, 37 polymer permeation by 347 solubility in blood and tissues 50 et seq solubility in liquids 46 van der Waals constants 38

gastric volume, antacid effects 391 (table) gastric emptying 390, 454 gastric motility 390 gastrointestinal tract

drug absorption from 386 structure of 386-388

gels antibiotic-loaded 321 of block copolymers 322 cellulose derivatives 334 heterogels 321, 322 hydrogels 326-329, 344

556 Index

gels (continued) of poly(vinyl alcohol) 320 syneresis of 322 type I and type II 320 of water-soluble polymers 315, 319-323

gel points, PVA 320 (table) Gelofusine 74 Gelusil 474 Gibbs adsorption isotherm · 201 et seq glass, adsorption on 329-331, 475, 476 glass transition temperature 311, 344 (table) globulins 479 glutethimide 19, 24 7 glycerogelatin bases 445 glyceryl trinitrate

affinity for plastics 476, 477 buccal absorption of 392, 393, 394 patches 537

glycoproteins 325 glycosaminoglycans 324 Gouy-Chapman layer 229 graft copolymers 309 gravitational settlement 430 griseofulvin

absorption of 278, 390 eutectic mixtures of 30, 31 micronisation and biological activity 25 solubilisation of 247

guaran 327 gum arabic 335, 336 gum tragacanth 336 gums

locust bean 327 Plantago a/bican seed 323 psyllium seed 328 viscosity of solutions 332, 333 xanthan 327

gut-asssociated lymphoid tissue see GALT

haemodialysis 223 haemoglobin 50-51, 52, 502 haemolysis 74, 249 haemoperfusion 223 half-life of reaction 112, 114, 115, 141 halothane 40, 52, 53, 77 Hamaker constant 256 Hammett relationship 102 heat sterilisation and stability 129 HendersonHasselbalch equation 197 Henry's law 47, 53 heparin 324 heterogels 321 hexoestrol 247 hildebrand units 173 HLB 266 et seq

effect of electrolyte 270 of emulsifiers of natural origin 270 (table) and emulsion stability 268-270 group contributions 269 of oils 269 and particle size 270 of polysorbates 240 (table) of sorbitan esters 240 (table) of surfactants 268 (table)

homopolymers 308 homotropine hydrolysis 112, 113 HPMC see hydroxypropylmethylcellulose human albumin, recombinant 519 human Iispro 524 human milk 196, 197 humidity, and stability 148, 149 Humulin 524 hyaluronic acid 324, 326 hydrated compounds 56

hydrates 18 et seq of ampicillin 21 dissolution rate of 20 of glutethimide 19 of oxyphenbutazone 20 (table) solubility of 19 of theophylline 19

hydration 159 et seq hydrophobic 161 of hydroxyethylcellulose 335 of ionic species 159, 160 of macromolecules 318 of non-electrolytes 159 and viscosity 318

hydration numbers 160 hydrocortisone 20, 407 hydrogels 326-329, 344 hydrolysis

acidbase-catalysed 102, 124-127 of amides 102 of drugs 101 et seq, 398 of esters 101 of lactams 102, 117, 119

hydrophilelipophile balance see HLB hydrophobic bonding 225 et seq, 297 hydrophobic character, amino acids 500 (table) hydrophobic hydration 161 hydrotropic salts 162 hydrotropy 162 1-hydroxyanthraqninone chelate 464 hydoxynaphthoates 182 hydroxypropylmethylcellulose (HPMC) 355, 420,

421

ibuprofen 42, 43 ice structure 226 ideal gases 36 ileum 387, 388 immersional wetting 28, 295, 296 immunoglobulin, Fe fragment 499 implants 363 in vitro-in vivo correlations 531, 533 in vitro tests 527 et seq inclusion complexes 176, 177, 470, 471 incompatibilities 449 et seq

and suppository bases 445, 446 tables of 486 et seq

indomethacin ester 138 inertial precipitation 432 infant formula 76 infrared spectra of polymorphs 16 injection

intradermal 396 intramuscular 395 et seq intrathecal 446 intravenous 395 et seq subcutaneous 395 et seq

inhalation therapy 428 et seq initiation of reaction 103 inorganic solutes, solubility of 161 insulin

adsorption of 329-331 fibril formation 523 formulation of 400-403 formulations 522 (table) human soluble 402 injections of 401 (table) pharmacokinetics of 522 (table) precipitation of 522 solubility 403

intensive properties 69 interactions 449 et seq

anionic-cationic 459-461 between cells 299 of drugs 449 et seq, 485 et seq (table)

of drugs and cyclodextrins 470, 471 of drugs and plastics 476, 477 of drugs and suppository bases 445, 456 ion-exchange 4 71 ionic 459-461

interfacial polymerisation 358, 359 interfacial tension 201, 274, 334 (table) interleukin 1-,8, ribbon diagram 499 internal energy 58 intestinal absorption 379 intradermal injection 396 intragastric pH 384, 391, 454 Intralipid 74, 282 intramuscular injections

absorption of drugs from 395-397 clearance from 397 (table) formulation of 397-400 particle size and 23

intrathecal administration 446 intravenous fat emulsions 281 intravenous fluids, tonicity 74 (table) intravenous giving sets 476 intravenous injections 395 et seq intrinsic dissolution 20 intrinsic viscosity 317 inulin 396 iodine, solubilisation of 248 iodophors 248 ion binding, macromolecules 325 ion-exchange interactions 471 ion-exchange resins 348 et seq, 351 (table), 471 ion pairing 384-386, 459 ionic product of water 83, 85 (table) ionic species, hydration 159, 161 ionic strength

calculation of 66, 67, 132 defined 66 and drug decomposition 132, 133

ionisable drugs, partitioning 184 ionisation

of amphoteric electrolytes 88 of drugs 64, 80 et seq and partitioning 184, 185 percentage 86, 87 (table), 88 pH and 80 et seq, 163 of polyprotic drugs 88-90 of water 83, 85 (table)

ionisation constant see dissociation constant Ionosol B 461 ions

activity of 64-67 chelation of 463 chemical potential of 72

iontophoresis 414 iron salts, chelation of 463 irreversible processes 61 isoelectric points, proteins 501 (table) isoflurane 40, 77 Isogel 330 isomerisation 105-107 isotactic copolymers 310, 311 isotherms, adsorption 216-220 isotonic saline 57 isotonic solutions, preparation 79 isotonicity 74 Itrafusin 74

jejunum 387

kaolin, adsorption by 216, 222, 473 Kaopectate 473, 474 Katonium 351 kidney tubule 456

kinetics of drug decomposition in ointments and creams 135

Index 557

in solid dosage forms 120-122, 135-139, 146 in solution 109 et seq in suspensions Ill, 145

krypton 52

lacrimal fluid (tears) 417 pH of 81,95

lamellar phase 234 Langmuir adsorption isotherm 216-218 Langmuir constants 217, 218 (table) Langmuir trough 208 Lanoxin elixir 474 law of conservation of energy 58 law of mass action 228, 480 laxatives, bulk 328 LD50 26 Le Chatelier's principle 47 lecithin monolayers 214 LHRH 438, 475, 476 light, and drug decomposition 107, 108, 139, 147 lignocaine, eutectic 32 lincomycin, absorption of 4 74 Lipofundin 74 lipophilicity

and absorption 376 et seq and log P 188, 190 and protein binding 482 and toxicity 193

liposomes 237, 238 liquid crystals 233 et seq, 277 liquid impinger 546 liquids, surface and interfacial tensions 201 (table) local anaesthetics

adsorption of 219, 220, 224 surface activity 207

locust bean gum 327 logP

and biological activity 186, 376, 377 calculation of 195, 196 of drugs 189 (table), 421 (table) and bacterial growth inhibition 193 and intrathecal drug administration 446 permeability and 422 pH and 188, 190 and peptide permeability 517 and protein binding 482 and sublingual absorption 394 of transport systems 377 (table) using 188-197

Lowry-Bnmsted theory 81 Lundelius' rule 220 lyofoam 343 lyophilisation, proteins 519 lyotropic liquid crystals 234

M-cells 23 Maalox 454 Macrodantin 26 macrogols see polyoxyethylene glycols macromolecules 308 et seq

adsorption of 328 as adsorption suppressants 328-331 binding of ions 325 hydration of 318 interactions with drugs 461 as stabilisers 260

magnesium chelates 465 magnesium trisilicate 222 magnetic resonance imaging 469 mannitol 397 mass action theory of micellisation 228 matrices 355 maximum additive concentration 242

558 Index

mecamylamine 455 mecillinam degradation 128, 129 medazepam 477 mefenamic acid 17 melting point

of polymorphs 14 and solubility 155, 156

melting of solids 60 membranes see biological membranes Methocel 334 methotrexate 446 methoxyflurane 77 methyl dopate 101 methylamphetamine 41, 42 methylcellulose 332-333 Meyer-Overton hypothesis 49, 50 micelles

and drug stability 134, 135 formation of see micellisation inverted 230 polymeric 322 structure of 229-230

micellisation 224 et seq causes of 225 of block copolymers 322 of drugs 230, 231 and hydrophobic bonding 225 et seq theories of 228 and water structure 227

microbial spoilage, of emulsions 279 microcapsules 357 et seq microdissociation constants 88, 89 microelectrophoresis 288 microemulsions 272 et seq, 276 micronisation 25 micropatches 428 microspheres 357 et seq microvilli 387 milk (human)

drug distribution into 196 (table) milk/plasma ratio 196 pH of 197

Miller indices 6-8 milliequivalents 57 mixed solvent systems

dilution of 457 solubility in 174

moisture, effect on stability 135, 136, 147 molal activity coefficient 64 molal elevation constant 46 molal freezing point constant 46 molality

defined 56 mean ionic 65 and mole fraction 46, 71

mole fraction 46, 57, 71 molecular size, i.m. route 396, 397 (table) molecular weight

number and weight average 312, 314 of dextran fractions 314 and solvent penetration 316 and nasal absorption 440 and viscosity 319, 337

monolayers as cell membrane models 214, 215 experimental study of 208, 209 insoluble 208 et seq penetration by drugs 214 pharmaceutical applications of 213 polymer 211 states 209-211 temperature effects 212

morphine degradation of 103, 104 dissociation of 89

mucilages 335 mucoadhesives 342 (table) mucous membrane, nasal 440 mucus 387 multiblock coploymer 309 multiple emulsions 270 multistage liquid impinger 546 muscle, pH of 81

nalidixic acid 467 nanoencapsulation 361 naproxen absorption 455 narcosis 49 nasal mucous membrane 440 nasal route 437-441 nasolacrimal duct 416 natural gums 335 neat phase 234 nebulisers 435 neomycin sulphate activity 421 (table) Neoral 276 Nemst equation 10 neurotoxicity 192-193 neutralisation, by antacids 453 (table) Newtonian flow 317 nicotine 394 Nicotinell 368 nifedipine 366 niosomes 237 nitrazepam decomposition 102, 117, 147, 148 Nitro-Our 368, 369 Nitroderm TIS 368 Nitrodisc 368, 369 nitrofurantoin 26, 456 non-aqueous suspensions 294 non-electrolytes

hydration of 159 membrane penetration of 375

non-ideal gases 36 et seq non-ionic surfactants

cloud point of 232, 248, 249 critical micelle concentrations of 204, 232 (table) HLB values 240 (table), 268 (table) micellar properties of 239-241 micellar structure of 230 phase diagram of 235, 243 solubilisation by 245, 246, 248, 249 vesicle formation by 237

norfloxacin 467 Normacol 330 Novolin 523 Noyes-Whitney equation 10, 21 nucleation 10 Nutriflex 74 nylon 6, 10 361 nylon 6 powder 221

ofw emulsions 253, 264-266 octanol 186 octanol-water partition 184 et seq Ocusert 424 17 ,8-oestradiol 246 ,8-oestradiol diacetate monolayer 212 oestrone 246 oftoxacin 467 oils

anaesthetic solubility in 49 HLB values 269 oxidation of 103

ointments 408, 409 dilution of 135, 412 of pilocarpine 419, 420

oleogels 294 oleyl alcohol, monolayers 211 oligomers 308

oligonucleotides 496 ophthalmic formulations 418 et seq oral absorption 386 et seq oral cavity 392 oral mucosal route 392 (table) oral rehydration therapy (ORT) 77, 78 oral route 386 et seq order of reaction 109 et seq, 142 Oros 364, 366 ORT see oral rehydration therapy orthorhombic crystal forms 9 osmolality and osmolarity

of anaesthetic solutions 77 (table) of blood serum 77 of drug formulations 73 (table) of druginfant formula mixtures 76 (table) of eye drops 420 of intravenous preparations 75 (table)

osmotic coefficient 73 osmotic pressure

and activity 73 clinical relevance of 74 et seq and colloid stability 262 defined 72 of drug solutions 72 et seq and oral rehydration therapy 77-79

osmotic pumps 364 osmotic tablets 364, 366, 367 Ostwald solubility coefficient 47, 49, 51 Overton-Meyer theory 187 oxidation

of cephalosporins I 06 of drugs 103-105 of morphine I 04 of oils and fats 103 and pH 129 of pilocarpines 105, 106 prevention of I 05, 134, 513 of proteins 512-514 of tetracyclines I 05 of vitamin A 107

oxygen and drug stability 134, 139 permeation 347 solubility in blood 50

oxygen tension 50 oxyphenbutazone 20 oxytetracycline

solubility 165, 167 (table) structure 168

P. mirabilis 69 packaging 146 packaging materials 213 palisade layer 230 parabens 477 paracetamol 137, 443 parallel reactions 117 parenteral medication 396 parenteral solutions, pH of 168 (table) partial molar free energy see chemical potential partial molar quantities 69 partial molar volume 69, 70 particle size

of aerosols 429 et seq, 543 et seq and bioavailability 23 biopharmaceutical importance of 22 et seq and deposition in respiratory tract 429 et seq pharmacopoeial control of 24, 25 (table) and toxicity 25, 26

particles adhesion of 294, 296 deposition in respiratory tract 429-434 uptake in the GI tract 22, 23, 386

partition coefficients 183 et seq of anaesthetics 49-54

Index 559

and bacterial growth inhibition 193 and biological activity 186 et seq calculation of 195, 196 chloroform/water 190 of chlorpromazine 385 defined 183 heptane/glycol 517 hexane/water 195 (table) and inclusion complexes 4 70 liquid/gas 49 and membrane transport 3 77 and micellar solubilisation 246 and neurotoxicity 194 oil/gas 49, 54 and penetration into red blood cells 190 pH dependence of 188 and peptide permeability 517 and protein binding 482 and sorption by PVC 195 uses of log P 189-197 waterfgas 54

partitioning 183 et seq and anaesthetic action 192 and bacterial growth inhibition 193 of drugs into erythrocytes 190 of drugs into human milk 196 free energy of 184 of ionisable species 184, 185 and neurotoxicity 194 into PVC 195 and solute association 184 of sulphonamides 190

particulate absorption 22, 23, 386 PAS granules 475 PDMS see polydimethylsiloxane pectin 337 pellets, gastric emptying 390 penetration of drugs

into aqueous humour 190, 192' into brain 192 into cerebrospinal fluid 190, 192 and protein binding 484 into red blood cells 190

penicillamine 469 penicillins

hydrolysis of 102, 135 polymerisation of 109 protein binding of 483, 484 (table)

pentanol isomers 155 (table) pentobarbitone potency 26 (table) peptides 493 et seq

adsorption of 475 definition of 493 delivery of 521 stability of 504 et seq transport of 516-519

percutaneous absorption 413 (table) permittivity see dielectric constant permeability

coefficient of 422, 517 and log P 422 of microcapsules 362 (table) and pHpartition hypothesis 377-380 of polymers 345

permeability coefficients of ,8-blockers 422 of peptides 517

pH and absorption into aqueous humour 418 and absorption of drugs 377 et seq and adsorption 220, 221 of body fluids and sites 81 (table) and buffer capacity 94-96

560 Index

pH (continued) calculation of 90 et seq and drug decomposition 123 et seq and drug interactions 450 et seq of eye drops 418 of gastrointestinal tract 380 (table), 452 in vitro and in vivo effects 450-457 and intestinal absorption 379 (table) and ionisation of drugs 80 et seq, 163 of membrane surface 381 and monolayer permeability 214 of parenteral solutions 168 of protein formulations 508 and solubility 163 of stomach 391 urinary 81, 455

pH-partition hypothesis 377 et seq phagocytosis 298 pharmacopoeial dissolution tests 528-530 phase diagrams

non-ionic surfactants 235, 243 proteins 503 solid dispersions 30, 31, 32 solubilised systems 242, 243 three-component 242, 243, 310

phase separation model of micelle formation 228

phenobarbitone bioavailability 23 elixir 75 intravenous preparation 75 polymorphic forms 14, 15 solubility in mixed solvents 174 suspensions of 23

phenothiazines adsorption of 218 inclusion complex 470 particle size and activity of 25 photochemical decomposition of 107, 108 pK. values 172 (table) surface activity of 207 water solubility 172 (table)

phentolamine, degradation of 132, 133 phenylbutazone 471

binding 482 phenyltoloxamine 350 pholcodine 350 phosphate solubility 451 phosphatidylcholine (lecithin) 374 phospholipids

monolayers of 214 structures of 374 vesicles of 231

phosphoric acid, ionisation of 89 photochemical decomposition 107, 108, 139 physostigmine 101 pilocarpine

absorption of 418-420 hydrolysis and epimerisation of 105, 106, 118 structure of 420

pK. defined 82 of drugs 83-85, 379 of proteins 90, 501 (table) see also dissociation constant

plasma expanders 337 plastic flow 293 plasticiser 344 plastics 311

drug interaction with 476, 477, 478 (table) partitioning of drugs into 194, 195

platelets 304 Pluronic surfactants 322 poloxamers 322 polyacrylamide 291, 313

poly(acrylic acid) 324 polycarbophil 351 polydimethylsiloxane 305, 306 polydispersity 311 polyelectrolytes 329 polyethylene glycols 68, 137 poly(ethyleneimine) 324 poly(glycolmethacrylate)s 321 poly(HEMA) 321 polyions 461 polymer matrices 355 et seq polymeric depots 356 (table) polymerisation degradation 108 et seq polymers 308 et seq

amorphous 345 bioadhesivity of 342, 353 as bridging agents 292 branching of 309, 310 block copolymers 310, 321, 322 complexes of 323-325 crosslinked 320, 321 crystalline 345 crystallinity of 344 definition of 308-311 diffusion in 345, 346 drug binding by 347-348 film coating 354 as flocculating agents 291 free energy of dilution of 327 gels of 319-323 glass transition temperature of 311, 344 interactions with water 326 matrices of 355 et seq, 364 membranes of 344 et seq molecular architectures of 309 molecular weights of 311, 312, 314 monolayers of 211 morphology of 315 permeability of 345 et seq phase behaviour of 310 polydispersity of 311-314 rate-limiting membranes solubility of 316 solvent penetration of 316 structural formulae of 313, 314 viscosity of 317-319, 332 water-insoluble 344 et seq water-soluble 316 et seq, 331 et seq, 342 as wound dressings 343

polymorphic drugs 14, 15 (table) polymorphism II et seq

analytical implications of 16 pharmaceutical implications 14 of theobroma oil 441

polymorphs, melting points 14 polyoxyethylene glycols (macrogols)

and dissolution 341 and protein solubility 503 structure and properties 341 suppositories of 137, 138, 441, 444, 445

polypeptides 493 et seq definition 496

polyprotic drugs 88 polysaccharides 325 polysorbates

critical micelle concentrations of 240 (table) HLB values 240 (table) solubilisation by 245, 248, 249 structures 241

poly( vinyl alcohol) (PV A) 313, 420, 421 poly(vinyl chloride) (PVC)

sorption by 194, 195, 476, 477, 478 (table) structural formula 313

polyvinylpyrrolidone (PVP) 323, 339, 340, 420, 421

povidone 137 powders

contact angles 29 (table) wetting of 26-29

precipitation and pH 10, 164, 167, 168 of proteins 506 in vivo 457

prednisolone 20, 129 preservatives

availability in emulsions 279, 280 (table) fate of 194

pressure and gas solubility 47 units 36

prismatic crystals 8 procaine, eutectic 32 prodrugs 423 Progestasert 363 progesterone 407 promazine adsorption 473 propagation of reaction 103 propellants 38-40, 434 prostaglandin E1 282, 283 prostatic fluid 485 proteins 493 et seq

adsorption of 475, 506, 507 aggregation of 506 a-helix 497 {3-elimination of 514 /3-sheets 498 binding of 477 et seq

and antibiotic action 483, 484 of cephalosporin• 484 (table) and drug interactions 488-491 (tables) equations for 480 and lipophilicity 482-484 of penicillins 484 (table) of tetracyclines 190 (table) thermodynamics of 481

definition of 496 deamidation of 509-511 denaturation of 505, 507 diffusion of 516, 517 formulation of 516 et seq hydration of 507, 508 hydrodynamic properties of 517 (table) hydrophobicity of 498 microspheres of 362 monolayers of 211 oxidation of 512-514 pK. values 90 proteolysis of 514 racemisation of 514 routes of delivery 521 (table) stability of 504 et seq stability testing of 514-516 structure of 496 transport of 516

proteolysis 514 pseudoplastic flow 293 pseudopolymoprhism 13, 14 psyllium seed gum 328 Pulvinal 436 PVA see poly( vinyl alcohol) PVC see poly( vinyl chloride) PVP see polyvinylpyrrolidone pyloris 387

quinolones 467

racemisation of proteins 514 Raoult's law 38, 39, 48

rate constant 110 of complex reactions 115-120 of dissolution 21 factors affecting 123 et seq of first-order reactions 110-113

Index 561

of second-order reactions 113, 114 of solid dosage forms 120-123 of third-order reactions 114 of zero-order reactions 110, Ill

rate-limiting membranes 363 rate of solution !53 rational activity coefficient 64 reaction rate

excipients and 136, 137 ionic strength and 132, 133 moisture and 135, 136 oxygen and 134 pH and 123-129 solvent and 133, 134 surfactants and 134, 135 temperature and 129-131

reactions complex 115-120 consecutive 119 first-order 110-113 order of 109 et seq parallel 117, 118 reversible 116 second-order 113, 114 third-order 114 topochemical 120 zero-order II 0, Ill

rectal absorption of drugs 441 et seq rectal cavity 442 red cells see erythrocytes registration 147 regular solution theory 171 rehydration solutions 76-8 renal tubules and pH 456 renal reabsorptuion 456 reservoir systems, ophthalmic 323, 424 Resinat 351 Resonium A 351 respiratory tract therapy 428 et seq reversible reactions 116 reversible processes 60 rheology

of blood 302-304 characteristics of products 537-540 of emulsions 283-285 of suppository vehicles 443, 445 of suspensions 293, 294

riboflavin, decomposition of 143, 144 rifampicin 4 7 5 rotating basket method (dissolution testing) 528-529 rotating paddle method (dissolution testing) 529 Rotohaler 435 routes of delivery, proteins 521 (table)

S. aureus 69 saline, normal 57 saliva, pH of 81 salting in 162 salting out 162, 503 saturated solutions 153 SchulzeHardy rule 260 scopolamine patch 413 second law of thermodynamics 59, 60 second-order reactions 113 sedimentation

of aerosol particles 431 of suspensions 286, 287

self-bodying emulsions 277 semen, pH of 81 semipermeable membranes 72

562 Index

semisolid bases 409 semisolid dosage forms 135 semisolid emulsions 277 septrin infusion 177-179 serum albumin 478, 479, 482, 483 Setschenow equation 162 shape effects and viscosity 318 shelf-life 139 silica oleogels 294 silicone polymers 352 skin penetration 403 et seq smectic states 235 sodium carboxymethylceUulose 334 sodium cromoglycate 428, 429, 435 sodium dodecyl sulphate 233, 238, 239 sodium Iaury! sulphate see sodium dodecyl sulphate Softens 321 solid dispersions 29 et seq solid dosage forms

stability of 135 et seq, 120 et seq stability testing of 146

solid solutions 29 et seq solid state 5 et seq solubilisation 241 et seq

of barbiturates 245 (table) of benzoic acid 248 (table) by bile salts 247 by cyclodextrins 174-177, 470 and drug decomposition 134, 135 factors affecting 244 et seq of iodine 248 location of solubilisate 243, 244 maximum additive concentration 242 and partition coefficient 246 pharmaceutical applications 248 of steroids 246 (table) of vitamins 248

solubility !52 et seq of acetanilide derivatives !57 (table) of acidic drugs 163-165 of alcohols in water 155 (table) of amphoteric drugs 166 of anaesthetic gases 49, 51-54 of basic drugs 164-166 and biological activity 181 boiling point and 155 of clobetasol propionate 412 (table) of crystal hydrates 19, 20 and drug release 443, 444 of erythromicin 180 expression of !53 of drug salts 179 (table), 180 (table) of drugs !52 et seq factors affecting !53 et seq of gases in blood and tissues 50 et seq of gases in liquids 46 et seq of gases in plastics 346 of glutethimide 19 of inorganic solutes 161 in mixed solvents 174 measurement of 170, 171 melting point and 155, !56 model of solution process 153, 154 and molecular surface area 154-155 of oxygen in blood 50-51 of pentanol isomers !55 (table) of peptides 50 I and pH 163 et seq of phenothiazine& 172 (table) of polymers 316 problems 177-182 of proteins 501 of solvates 18 et seq of steroids 157, !58 (table) structural features and !55 et seq

substituent& and 156-157 of sulphonamide& !56 (table) of tetracyclines 454 of theophylline 19 and toxicity 182 in TPN solutions 451

solubility parameter 171 et seq and biological processes 173 and release rate 352, 353 of solvents 173 (table)

solubility product 161, 162 (table) solutions

activity of 64 et seq concentration units 56, 57 defined 153 isotonic 74-79 solid 29

solvates 18 absorption rate of 20 beclomethasone 18 cephaloridine 18 dissolution rate of 20 fludrocortisone 18, 19 and solubility 18 succinylsulphathiazole 18

solvation see hydration solvents

activity of 67 et seq amphiprotic 82 and drug decomposition 133 et seq mixed 457 polymer penetration of 315, 316 solubility parameters of 173 (table)

sorbic acid 224 sorbitan esters

HLB values 240 (table) structures 241

sorption 215, 216 into PVC 195 (table) of preservatives 193-195

Spans see sorbitan esters spinal cord 446 spironolactone

crystal forms 13 hydrates 18 unit cells 12

spontaneous processes 61 spray coating 358, 360 spray polycondensation 360 spreading wetting 28, 295, 296 stability

of colloids 255 et seq of drugs 101 et seq of emulsions 264-266 factors affecting 123 et seq of proteins 504 et seq of suspensions 286

stability testing 139 et seq protocols for 147-150

standard state 64 star block copolymers 309 Staudinger equation 319 steric stabilisation 262 Stern plane 257, 258 Stern layer 229 steroids

monolayers of 210 polymorphism of 14, 15 skin permeability 407 solubility of 157, 158 (table) solubilisation of 246 (table) structures of 158, 407, 408

Stokes-Einstein equation 98 stomach 387 stratum corneum, models 404

structure breakers !59, 160 structure makers !59, 160 subcutaneous injection 395 et seq sublingual absorption 394 sugar paste 68, 70 sugars 519 sulphathiazole 156, 341 sulphonamides

binding of 483 membrane penetration of 376 polymorphism of 14, 15 log P values 188-190 solubility of !56 (table)

supersaturated solutions !53 supersaturation 9 suppositories

in vitro evaluation 532, 534 release of drugs from 443

suppository bases 443 et seq and drug stability 137, 138 incompatibility with drugs 445, 446

surface-active agents see surfactants surface activity

of cellulose derivatives 334 (table) of drugs 206-208 and hydrophobicity 205-207 of surfactants 200 et seq

surface area at air/water interface calculation of 204, 205 of cholesterol 210 of fatty acids 210

surface charge 257, 258 surface excess concentration 203 surface films see monolayers surface free energy 200, 20 I surface pH 381 surface potential 257, 258 surface pressure 209 surface tension

of cellulose derivatives 334 (table) defined 200, 201 of liquids 201 (table) lowering by surfactants 200 et seq units of 201

surfactants 199 et seq adsorption of 215 et seq, 296 area per molecule 205 classification of 200 critical micelle concentration 205, 224, 230-233,

240 and crystal growth I 0 and drug stability 134, 135 and emulsion stabilisation 264 et seq HLB values 240 (table) and membrane permeability 421 micelles of 224 et seq phase properties 234, 235 properties of 238 et seq solubilisation by 241 et seq surface activity of 200 et seq vesicles 233, 237 and wettability of powders 29

suspensions 285 et seq adhesion of particles 294-297 caking of 285-291 extemporaneous 292, 293 flocculation of 285-291 hydrolysis of drugs in Ill photomicrographs of 253 release from 411 rheology of 293, 294 stability of 286 et seq stability testing of 145 zeta potential of 288 zone sedimentation of 287

sweat, pH of 81 swelling interface number 326 switching mechanism 328 syndiotactic copolymers 310, 311 syneresis 322 Synthaderm 343 syringeability test 537, 538

Index 563

tablet excipients and drug stability 136 tabular crystals 8 tears see lacrimal fluid temperature

adsorption and 222 drug stability and 129-131, 138, 141 gas solubility and 47, 53 ionisation of water and 85 (table) micellar properties and 232, 233 partition coefficients of gases and 54 solubilisation and 247, 248 solubility and 47, 53, 54 theta 327 vapour pressure and 41 et seq

tensile strength, polymers 344 testosterone solubility 340 tetracaine I 0 I tetracycline

absorption of 454, 462 antacids and 454 calcium binding by 464 (table) chelation of 462-464 isomerisation of 105 lipid solubility 188 lipophilicity of 188 log P values 190 (table) microdissociation constants 90 partitioning of 190 pH effects and 450 pK. values 465 protein binding of 190 solubility of 180 (table), 181, 454 structures of 465 salts 180 (table)

theobroma oil 441 theophylline

complexation 469, 470 elixir 75, 76 solubility 19

therapeutic proteins 493 (table) thermodynamic activity see activity (thermodynamic) thermodynamics 58 et seq

of binding 481 of dilution of polymers 327 and chemical equilibria 61-63 and colloid stability 260-263 of interfaces 202-204 laws of 59-61 of micellisation 225 of partitioning 185 of protein binding 481 of vaporisation 41-46

thermotropic liquid crystals 235, 236 theta temperature 327 third law of thermodynamics 61 third-order reactions 114 thixotropy 295 thrombus formation 304 tonicity 74

see also osmolality; osmolarity topical preparations 3, 408 et seq

consistency of 537, 539 dilution of 412 in vitro testing of 533, 535-537

topochemical decomposition 120, 121 total parenteral nutrition (TPN) 451

564 Index

toxicity of drugs 182 (table) and lipophilicity 193 and particle size 25, 26

toxins, adsorption 222 TPN see total parenteral nutrition tragacanth 336 transdermal delivery 403 et seq

devices for 368 (table), 369, 370 transdermal patches 3, 412-415

adhesives for 353 (table) transdermal penetration, and ultrasound 415 transdermal products, in vitro testing 533, 535-537 Transiderm-Nitro 368, 369 Traube's rule 204 TRH analogues 438 triamcinolone 407, 408 triglyceride absorption 389 TrophAmine 451 Tweens see polysorbates two-phase systems 71

ultrasonic nebuliser 435, 439 ultrasound 415

and skin penetration 415 unit cells 6, 7 units of concentration 56-58 universal buffers 96 unstirred layers 381 urethra 427 urinary pH 81, 455

vagina 426, 427 vaginal delivery systems 426 vaginal rings 426, 428 valinomycin 215 Valium injection 399, 457 Yamin 74 van der Waals constants 38 (table) van der Waals equation 37 van der Waals forces 216, 227, 256 van't Hoff equation 63, 73, !39 vaporisers 40 vapour pressure

of aerosols 38-40 lowering of 44 solution composition and 38-41 temperature and 41 et seq

Veegum 223 vehicle effects, skin permeation 408 et seq vehicles, i.m.js.c. use 397 Ventodisk 438 Venturi nebuliser 435 vesicle-in-water-in-oil system 298 vesicles 23 7, 297, 298 villi 387 viscosity

of blood 302 of emulsions 283-285 of gum solutions 332, 335, 336

of oleogels 294, 295 and molecular weight 319, 337 of polymer solutions 317-319, 333, 340 of PVP solutions 340 relative 317 specific 317-319 of suppository bases 443 of suspensions 293, 294

vitamin E succinate !39 vitamins

decomposition of 139 isomerisation of 106 solubilisation of 249 (table)

Vitrimix 74 volatile anaesthetics, solubility 49

wjo emulsions 264-266 wfofw emulsions 264-266, 270, 273 warfarin 471, 477 water

activity 67 adsorption of 519 dissociation constant of 83, 85 (table) ionisation of 8 permeation 348 structure of !59, 225 et seq vapour pressure, and decomposition 136

water-soluble polymers 316 et seq, 331 et seq weak acids and bases

absorption of !90, 192, 378, 379 (table), 380 ionisation of 80 et seq, 378-380 partitioning of 183-185 pH of 90-93 solubility of 163 et seq

wetting adhesional 296 contact angle and 27 et seq immersional 28, 295, 296 spreading 28, 296

Wilson's disease 469 Witepsol H 443 wound dressings 343 wounds 68 Wruble method (dissolution testing) 528

xanthan gum 327 xenon 52 X-ray contrast media 193, 291, 459 xylose 68, 70

Young's equation 27, 28

zein 355 zero-order reactions 110 et seq zeta potential

and adsorption 297 and colloid stability 257, 258 and suspension stability 288-291

zinc insulin dimer 499 zinc chelation 468 zone sedimentation 287