Index

Note: page numbers in bold refer to main discussions in the text, those in italics refer to figures, tables and schemes.

a-helix 435

absorption of drugs 2, 334-5 antacids, effect of 398-9, 416 buccal 346-9

crystal polymorphism 18-19 delayed 415-16 eye application 367 from gastrointestinal tract 23, 341,

342, 343, 415-16 from injections 349-55 intranasal 383-5 mechanisms 346-7, 348, 349 of polymorphs 18-19 of solvates 21-2 predictive index 157 rectal 385-9 sublingual 346-9 topical application 359-60 vaginal 375-6 acceptor molecules 411 acetanilides, substituted 143-4 acetazolamide, extemporaneous suspension 259 acetylsalicylic acid see aspirin acid-base catalysis general 95, 114 specific 114 acid-base pair conjugate 76 acid-catalysis 94 acidic drugs acidic/basic drug mixtures 160-1 distribution in human milk 175 partitioning 165-6 pH effect on solubility 150-1, 152, 153

solubility 150-1 see also weakly acidic drugs acidity constant 77, 78-9, 79-80, 82 acids

Lowry-Bronsted theory 75-6 polyprotic 83 weak 77

activity (thermodynamic) defined 62

in topical preparations 361 of drugs 63-4 of solvents 65-6 activity coefficient 62

mean ionic 63-4 adhesion artificial bridging 265-6 cell 265, 266 polymers 302 solid-solid 472, 473 suspension particles to containers 262-3, 264, 265 adhesives, pressure-sensitive 311 adhesivity of dosage forms 472, 473,

474-5 adjuvants 2 administration routes buccal 346-9 ear 374-5 eye 366-74 inhalation 376-83 intramuscular 349-55 intrathecal 389-90 intravenous 405 nasal 383-5 oral 341-6

peptides/proteins 454, 455 rectal 385-9

self-regulating systems 354-5 subcutaneous 349, 349-55 sublingual 346-9 transdermal delivery 355-66 vaginal 375-6 adrenaline absorption into eye 371, 372

adrenocorticotrophic hormone

(ACTH) 383 adsorbate solubility 197-8 adsorbent, nature of 199 adsorbent-adsorbate interactions 199 adsorption 194-201 by antacids 201, 398, 416 drug formulation 200-1 effect on drug absorption 414-17 factors affecting 197-9

isotherms 194, 195 microbial cells 266-7 peptides 416-17, 441 pH 198-9 poisons 199-200 prevention 443 proteins 416-17, 441, 443 taste masking 200 toxins 199-200 water isotherms 452-3, 455 Aerosil 262 aerosols 230 deposition 377-8, 378-9 devices 380, 381, 382 experimental observations 379-80,

381, 382-3 particle size distribution 378, 475-7 pressurised 380, 382 propellants 37-40 agglomerated particles 254-5 aggregation drugs 208

latex particles 254-5 peptides/proteins 441, 442-3 albumin 419-20 binding of drugs 420, 423 insulin adsorption prevention 292, 293

recombinant human 452, 454 alcohols branched-chain, solubility 142, 143 long-chain, antifoam action 270 alginates 126, 297 alkyl sulfate, ion pairing 341 aluminium chloride, flocculation of suspensions 257, 258, 259 aluminium hydroxide 398 Alza Ocusert 373-4 amino acids chemical degradation 445 folding 433, 434-5, 436 hydrophilicity 437-8 hydrophobicity 433, 436, 438 isoelectric point 437, 439 nomenclature 434 pKa 439 structure 434

p-aminobenzoic acid decomposition 111, 113 lipophilicity 169-70 aminoethyldextran-methotrexate complexes 300 p-aminosalicylic acid decomposition 111, 112 delayed absorption 416, 417 amiodarone, extemporaneous suspension 259 amitriptyline adsorption 196 adsorption isotherm 194 excretion 399 surface activity 184 amitriptyline hydrochloride 155 amphetamine excretion 399 amphipathic compounds 178-9 amphiphiles insoluble monolayers 185-7, 188,

189, 190 interfacial tension 179-80 micellar 207-8 surface tension 179-80 vesicle-forming 213 ampholytes ordinary 82 zwitterionic 82-3, 84 amphoteric drugs apparent partition coefficient

169-70 ionisation 82-3 pH effect on solubility 152-5 amphoterocin B 96, 97 ampicillin polymerisation 102 protein binding 424 anaesthesia/anaesthetic agents 39-40 gas solubility in blood/tissues 50-3 gaseous 43 intradermal 29-30 lipid solubility 52 local 201

Meyer-Overton hypothesis 48 minimum alveolar concentration 48

mixtures 40 oil solubility 48, 49 Ostwald solubility coefficient 46 sorption 201 unitary theory 48 vapour pressure 44 volatile 72 solubility in oil 48, 49 analgesics, buccal absorption 347 anhydrates 19

anion-exchange resins 307, 308 anionic compounds 81 antacids 398-400 and drug adsorption 201, 398, 416 polydimethylsiloxane antifoam agents 271

stomach pH 395, 396-7 antibiotics penetration of specialised sites 424-5

permeation into rubber stoppers

172 polyene 96

protein binding effects 423-4 antidepressants adsorption 196 tricyclic 156 antifoam agents 270 antihistamines, surface activity 185

antimicrobial agents 172

see also antibiotics antioxidants 97-8 Aqueous Cream 404 aqueous humour 369 Arrhenius equation 119, 120 protein stability 451 stability of drugs 128-32 solid state 126-7, 133 artificial throat devices 475-6, 477 aspirin 200 cholestyramine binding 414 cyclodextrin interactions 412 hydrolysis of suspension 104 with sodium bicarbonate 399 transacetylation with paracetamol 125 atropine adsorption 199 eye drop toxicity 374 phenobarbital mixture 404 Autohaler 382 autoxidation 95

P blockers eye drop toxicity 374 lipophilicity (log P) 370, 371, 372 Bacillus subtilis, growth inhibitory concentration 170, 172 bacteria adsorption to surfaces 266-7 growth 65-6 bactericidal activity 167 barbiturate-atropine complex 404 barbiturates contact angle 26, 27 solubilisation 223 barium sulfate 259 base-catalysis 94 bases, chemical Lowry-Bronsted theory 75-6 polyprotic 83 weak 77 bases, dermatological 359-60 basic drugs acidic/basic drug mixtures 160-1 distribution in human milk 174 partitioning 165-6

pH effect on solubility 151-2, 153 solubility 151-2 see also weakly basic drugs basicity constant 77, 78-9, 79-80, 82 P-cell, artificial 354-5 P-sheet 436 beclometasone 19 beclometasone dipropionate, intranasal 383 Becodisk 380, 382 bentonite 416, 417 benzalkonium chloride 216, 370 benzanilide, eutectic temperature 30-1

benzethonium chloride 263, 264 benzocaine dissociation 76 benzoic acid 416 absorption 338

adsorption by sulfadimidine 416 solubilisation 225, 226 benzyl alcohol absorption 338 bephenium hydroxynaphthoate 163-4

beta-elimination 445, 450 betamethasone skin penetration rate 358, 359 solubility 145, 146 betaxolol, ion-exchange resins 309 bile salts 225, 344 bioadhesion of polymers 302 bioavailability crystal polymorphisms 18-19 drug dissolution 22, 23 lipid o/w emulsions 249 particle size 23-6 phenobarbital 23, 24 solvates 21-2 biological activity lipophilicity 166 partition coefficients 166-8 biological membranes 331-41 buffers 339 composition 331-2 convective water flow 338 drug effects 339 fluid mosaic model 332, 333 ion pairing 340-1 permeability 333

pH partition hypothesis 335-7 pH

condition variability 337 at surface 336, 337-8 pores 333

solubility parameters 157 transport across 333 unstirred water layer 338-9 biological processes solubility of drugs 162-4 solubility parameters 157 biophase 43

chromatographic model 174 bishydroxycoumarin 408, 409

see also warfarin bismuth subnitrate suspension 257 block copolymers 219, 220 blood anaesthetic gas solubility 51-2 buffer components 89 colloidal system 267-9 flow characteristics 267-8 intramuscular/subcutaneous injection 351-2 gas solubility 49-53 pH 76

platelet adhesion 269 see also erythrocytes blood vessels, velocity gradients 269 body fluids, pH 76 Bohr effect 50 boiling point elevation 44, 45 of liquids 142 Boltzmann constant 234 bovine growth hormone (bGH) 443,

452, 455 Bravais lattices 9

bridging, artificial adhesion 265-6 bridging agents 265 Brij 97, phase diagram 221, 222 brompheniramine surface activity 184

Bronsted-Bjerrum equation 120, 122 Brownian forces 261 Brownian motion 265 brush border 344 buffer(s) biological membranes 339 liquid dosage forms 114 peptide adsorption prevention 417 protein stabilisation 443-4 universal 89 buffer capacity 88 buffer ions 414 buffer solutions 87-9

pH change 88 Bunsen's absorption coefficient 46 buprenorphine 346 buserelin 363, 365

caffeine 411, 412 caking 254, 256, 257 calcitonin 456-7, 458 calcium binding 288

complexing with tetracyclines 407 solubility curve for total parenteral nutrition 395 calixarenes 160 capillary wall pores 350

weak electrolyte absorption 350-1 capsules, adhesivity 472, 474 carbomer 302

carbon haemoperfusion 200 carbophil 302

Carbopol see carboxypolymethylene carboxymethylcellulose 291 carboxypolymethylene 293, 294 carmustine, vapour pressure 42 cartilage, hyaluronic acid interaction with proteoglycans 287 cascade impactor 475, 476 cation-anion interactions 402-5 cation-exchange resins 307, 308 cationic compounds, percentage ionisation 81 cavitation 365 cefalexin 414 cefaloridine 19-20 cefoxitin, lipid o/w emulsion 249 ceftriaxone, lipid o/w emulsion 249 cell adhesion 265, 266 cell-cell interactions 265-6 cellophane membranes 333-4 cellulose derivatives 295-6 microcrystalline 303 cellulose acetate(s) 191, 321, 322

hydrophilicity 306 cellulose acetate butyrate 191 cellulose acetate phthalate 191, 321 , 322

cellulose acetate stearate 191 cephalosporin ester isomerisation 99 cephalosporins, protein binding effects 423-4 ceruminolytic agents 375 cetomacrogol 218, 222 cetrimide 216, 217

ophthalmic formulations 370 chain processes 95-6 charcoal activated 200, 415 charge-transfer interactions 410-11 Le Chatelier's principle 149 chelation 405-10 chemical decomposition kinetics in solution 102-10 kinetics of solid forms 110-13 chemical deposition of drugs 94-102 chemical potential 66-9 component in solution 67, 68, 69 component in two-phase system 67, 68, 167 chemical structure 4

and drug stability 94-5 chemisorption 195 chitosan 298, 302

DNA interaction 459 chloramphenicol in aqueous humour 369

suspensions 263 chloramphenicol palmitate 18-19

wetting 27-8 chloramphenicol-urea eutectic mixture 29 chlordiazepoxide hydrolysis 110 chlorhexidine acetate ophthalmic formulations 370 chlorhexidine solubility 162 chloride ion secretion 73 chlorocresol 250

morphine injection 403 chlorofluorocarbons (CFCs) 37-8, 382

chloroform, partial pressure 47, 48 chlorothiazide 413, 414 chloroxylenol 225 chlorpheniramine adsorption 200 chlorpromazine affinity for plastics 306, 307 apparent partition coefficient 341 dipalmitoylphosphatidylglycerol interaction 191-3 morphine injection mix 403 pH effect on solubility 151, 152 photodegradation 100-1 solubility 141 surface activity 184 chlorpromazine hydrochloride 404-5 cholesterol biological membranes 332 monolayers 187, 188, 193 valinomycin interaction 193 chondroitin sulfate 288 chylomicrons 251-2 ciclosidomine Arrhenius plot 119, 120 hydrolysis 119, 120 stability 114-15 ciclosporin lipid o/w emulsion 249 microemulsions 247 cimetidine 397 ciprofloxacin chelation 409, 410 photodegradation 118, 119 circular dichroism 214 Clapeyron equation 40-1 Clausius-Clapeyron equation 41-3, 45

clindamycin 414 clobetasol propionate 362 cloud methods of particle size measurement 475 cloud point 209, 226 cloxacillin sodium 404 coacervation 314, 315-16, 319

DNA interaction with chitosan 459 coalescence 234 cocaine, ionisation percentage calculation 80 cocoa butter 385, 386-7 codeine sulfate hydrolysis 116-17 ionisation 117 pH-rate profile 115, 119

colchicine adsorption 200 colestyramine 413-14 colestipol 413, 414 colligative properties 69, 73 colloidal particles, interaction forces

231-5 colloidal systems blood 267-9 miscellaneous 263, 265 colloids 230-7 association 201 classification 230-1 continuous phase 230 disperse phase 230 DLVO theory of stability 231-2,

233, 235, 266 hydrophilic 230 lyophilic 230 lyophobic 230 repulsion between hydrated surfaces 235-7 stability 231-7 electrolyte effects 234-5 surface potential effects 235 theory 265-9 steric effects 235-6 see also aerosols; emulsions; suspensions complex reactions 107-10 complexation 403, 404, 405-10 concentration units 56-7 consecutive reactions 110 conservation of energy, law of 58 contact angle 26, 27, 28 contact lenses drug reservoirs 371, 373-4 hydrophilic 285 containers adsorption onto walls 201 amber glass for photodecomposition protection 102, 122 insulin adsorption 291-2, 293 intravenous 417-19 suspension particle adhesion 262-3, 264, 265 contraceptives, vaginal ring 376 contrast media 259

toxicity 171 copolymers 274, 275, 276

block 219, 220 copper, sequestering 410 cornea permeability 370 cortexolone 358 cosolvents 443-4 cosurfactants 245-6 counterions 207, 209 creaming 231 creams 359-60 active ingredient stability 123 shear conditions for spreading 254 stable oil-in-water 248

Cremophor 218

critical micelle concentration 180, 201

factors affecting 207-10 critical packing parameter 204-6

microemulsions 246 crospovidone 126 y-crystallins 438, 439 crystallisation 11-13

solvents 20 crystals dissolution 141 form 10-13 growth 11-12 habits 10-11

modification 12-13 hydrates 19-22 lattice 8, 17 Miller Indices 9-10 mixed 28

phase transformations 17 polymorphism 13-19 precipitation 12

pseudopolymorphism 15, 16, 19 structure 8-10 unit cells 8-9 see also liquid crystals cubic phase 210-11, 216 cubosomes 216

cyanocobalamin adsorption by talc 416

cyclodextrins 158-60 interactions 412-13 cyclopropane 52 cysteine 447, 448

cytostatic drugs, risk assessment 41-2

deamidation of proteins 445-7 Debye-Huckel layer see

Gouy-Chapman electrical double layer Debye-Huckel length 233 Debye-Huckel theory 63 deflocculating agents 256 deflocculation 254, 255 defoamers 269-71 delivery of protein drugs 451-5 deltoid muscle, blood flow 351 denaturation of proteins 441-2

prevention 443-4 dendrimers 274-5, 279

nanosystems 318 Deponit system 325, 326 deposition of aerosols 378-9 desferrioxamine 410 desmopressin 384 desorption of drugs 200 dexamethasone solubility 145, 146 dextran 298, 299, 300 clearance from i.m. site 350 crosslinked gels 303 dextranomer 303

dialkyldimethylammonium cationic surfactants 215 diazepam adsorption 200 formulation 352 lipid o/w emulsion 249 precipitation 401 thrombophlebitis 401 dicloxacillin 351 dietary fibre 288 diethyl phthalate 312 diethylhexylphthalate (DEHP) 173 diffusion aerosol deposition 379 bioavailability of i.m./s.c.

administered drugs 349-50 drugs in solution 89-90 Fick's law 90 in hydrogels 289 in matrices 313 in polymers 304-5 in skin 355-6, 361-2 diffusion coefficients 90 determination 357 peptides and proteins 452 digoxin 24 absorption 338 delayed adsorption 416 dimethicone 310 dimethylsiloxane 269 dimethyluracil 411, 412 diodoquin 409-10 dipalmitoylphosphatidylglycerol 191-3

diphenhydramine, surface activity 184

diphenylhydantoin adsorption 200 diphenylmethane drugs, micellar 207-8

disodium cromoglycate 376-7

phase diagram 403 dissociation constant 77, 78-9, 79-80, 82 macroscopic 83, 84, 85 microscopic 83, 84-5 dissociation of drug 425 dissolution bioavailability of i.m./s.c.

administered drugs 349-50 crystals 141 definition 140 particle size 24 solid drugs 22-3 dissolution testing 464, 465, 466-7 compendial 466 flow-through systems 466-7 pharmacopoeial 465, 466 rotating basket method 465, 466 distribution coefficients 164

see also partition coefficients disulfide formation 445, 450 DLVO theory of colloid stability

231-2, 233, 235 bacterial adsorption 266 DNA 458-9

dodecyltrimethylammonium bromide 209 donor-acceptor interaction 411 dosage forms 463-78 adhesivity 472, 473, 474-5 dissolution testing 464, 465, 466-7 rheological characteristics 471 tackiness 474 viscosity 474

in vitro evaluation 467-8, 469, 470-1

in vitro-in vivo correlations 467, 468

doxycycline, lipid solubility 168-9 drug-lipid interactions 191 drug-membrane interactions 193 dry-eye syndrome 367 duodenum 343

ear, drug administration 374-5 ear drops 375

econazole nitrate, oxidation susceptibility 96, 97 effective concentration 62 efflux mechanisms 334 Einstein equation 260-1 elastomers 274 electrolytes chemical potential 69 colloid stability 234-5 electrostatic forces 233, 265 electrostatic interactions 410 electroviscous effect 261 Embden-Meyerhof glycolytic pathway 50 Emla (Eutectic Mixture of Local

Anaesthetics) 29-30 emulsifier mixtures 240-2 emulsifying agents 220

choice 240-2 emulsions 230, 237-54 aged 254

biopharmaceutical aspects 249 coalescence 234 continuous phase 241 drug release 249, 362 fat 251-3

flow behaviour 253-4 globule size 254 hydrophilic component 249 lipophilic component 248-9 liquid crystalline phases 248 mean particle size 241 microbial spoilage 249-50 microsphere formulations 265 multilayer formation 248 multiple 237, 238, 242-3, 244 nonaqueous 243 oil-in-water 237-9

mass transport 250-1 viscoelastic 254 phase volume 253 preservative availability 249-50 relative viscosity 253-4 rheology 253-4 self-bodying 254 semisolid 247-9 stability 237-9 structured 247-9 vesicle formulations 265 water-in-oil 237-9 endocytosis 344 energy 57-8 cohesive density 156-7 free 60-1, 202

of transfer 166 internal (U) of system 58 law of conservation 58 enflurane-halothane mixture 40 enteral feed tonicity 71 enterocytes 23, 344 enthalpic stabilisation 235 enthalpy 58, 202, and colloid stability 235 of binding 421, 422 of fusion 59

of micelle formation 203 of vaporisation 59 see also molar enthalpy of vaporisation entropy 58-60, 202, and colloid stability 235-6 of binding 421, 422 of micelle formation 203 ephedrine 309

epidermis, transport through 355-6 epimerisation 98-9, 108 epinephrine see adrenaline equations 5

equilibrium constant 61 eroding systems 320, 321, 322 erythrocytes agglutination 266 binding of drugs 423 erythromycin 162 erythromycin lactobionate 404 Escherichia coli adhesion to kaolinite 267

essential oils, solubilisation 226 estradiol benzoate solubility 144, 146 estradiol diacetate surface pressure

187, 189 ethanol 158

ether, antifoam action 270 ethylcellulose 295 ethylene oxide, chain length 222-3 ethylenediamine 406 ethylhydroxymethylcellulose 296 ethylmethylcellulose 296 etorphine, buccal 347 eutectic mixture 28, 29

identification of drugs 30-1 ternary 31 eutectic point 28, 29 eutectic temperature 28, 29, 31 evaporation, monolayer resistance

190 excipients 2 protein stabilisation 443-4 solid drug stability 124-6 eye barrier systems 366 drug absorption 367-9 medication 366-74 reservoir systems 371, 373-4 structure 367

systemic delivery route 366-74 eye drops 370 systemic effects 374

famotidine 397 fat absorption pathways 344 intravenous emulsions 251-3 fatty acids long-chain 187 polyunsaturated 96 Ferguson's principle 166-8 Fick's first law 90, 304

transport through skin 355-6 film coatings, polymer 190-1, 311-12

first-order reactions 103, 104-5 passive diffusion of drug 349 pseudo 103, 105 flickering cluster model of water structure 202-3 flocculated systems 254, 255 flocculating agents 256 polymers as 259, 260 flocculation 254, 256 control 257 kaolinite 259 polycations 266

sulfamerazine suspension 257, 258, 259

X-ray contrast media 259 Flory temperature 290 fludrocortisone acetate 20 fludrocortisone pentanol 19 flufenamic acid 412 5-fluorouracil 243 fluphenazine decanoate 351 fluspirilene formulation 352 foam breakers 269, 270 foam preventatives 269, 270 foams 269-71 vaginal 376 formaldehyde hydrate polymerisation 102 formulation dilution of mixed solvent systems 401-2

formulation (continued ) eye administration 369-71, 372,

373-4 eye drops 370

intramuscular injection 352 ophthalmic 369-71, 372, 373-4 protein stability 443-5 proteins 451-5 solubility problems 160-4 subcutaneous injection 352 transdermal delivery 359-61 formulation of drugs adsorption problems 200-1 insulin 455, 456 Franz diffusion cell 468, 470 free energy 60-1, 202 of binding 421, 422 of micelle formation 203 of transfer 166 surface 179 free radicals chain reactions 96 solid drug stability 126 freezing point depression 44, 45 Freundlich equation 195, 197

gadobenic acid 410, 411 gadolinium chelation 410 gas laws 36 gases ideal 36-7 nonideal 36-7 solubility in blood/tissues 49-53 in liquids 46-8, 49 gastric emptying 345, 346

antacid effects 398 gastric glands 343 gastric juice 343 gastrointestinal tract absorption particulate 341, 343 rate 23 drug absorption 341-6 structure 343-4 gelatin nanoparticles 319 gels polymer 280, 284-6 structures 123 syneresis 286 vaginal 376 gentamicin sulfate 405 Gibbs adsorption equation 180-2 Gibbs free energy 60-1

see also free energy giving sets 173, 174

plastic components 417-19 glargine 457-8 glass amber containers 102, 122 peptide adsorption 417 platelet adhesion 269

glass transition temperature 276,

303-4 globulins 421 glutethimide solubility 20 gluteus maximus muscle, blood flow

351 glycerin 312 glycerogelatin 388 glycerol 158, 444 glyceryl trinitrate buccal 346-7 partitioning 172-3 poly(vinyl chloride) interactions 417-18

release from transdermal patches

470-1 sublingual 346

transdermal delivery 323-5, 326, 470-1 goblet cells 344

Gouy-Chapman electrical double layer 206, 207, 261 griseofulvin 24

lipid o/w emulsion 249 griseofulvin-succinic acid system 29

phase diagram 29, 30 growth hormone, bovine (bGH) 443,

452, 455 gum, natural 296-8 gum arabic 296-7 gum tragacanth 297 gums locus bean 290-1 Plantago albican seed 286 psyllium seed 291 xanthan 290 gut-associated lymphoid tissue (GALT) 23, 343

H2-antagonists 397 haemoglobin 49 oxygenation 50 solubility 438-40 haemoperfusion 200 half-life of reactions 104, 105 halothane lipid solubility 52 partial pressure 51 solubility 51-2 Hamaker constant 232 Hammett linear free energy relationship 95 Henderson-Hasselbalch equation 87 Henry's equation 256-7 Henry's law 46-7, 52 heparin, repeating sequence 287-8 heparin sodium 404 heterogels 285-6 hexamethylenediamine 317 histidine 447, 448 HLB (hydrophile-lipophile balance) system 217, 218, 239-42

group contributions 240 homopolymers 274, 276 honey, infected wound treatment 66 host-guest type interactions 160 hyaluronic acid 288

proteoglycan interaction 287 hydrates 19-22 hydration 146-9 heat of 149 hydrophobic 148-9 numbers 148 polymer solutions 282-3 hydrocortisone absorption rate 21-2 semisolid dosage forms 123 skin penetration rate 358, 359 hydrofluoroalkanes (HFAs) 37-8 binary mixtures 39-40 vapour pressure 38 hydrogels stability of active ingredients 123 swelling 289 hydrogen bonding 202 hydrolysis 94-5 hydrophilic drugs 184-5 hydrophilic regions of surfactants

178, 179, 208-9 hydrophilicity of amino acids 437-8 hydrophobic bonding 202-3, 410 hydrophobic drugs 26-7, 183-4 hydrophobic regions of surfactants 178, 179 chain length 222 structure 207-8 hydrophobicity of amino acids/peptides/proteins 433, 436, 438 hydrotropy 150 p-hydroxybenzoate, diffusion coefficients 90 p-hydroxybenzoic acid 222 hydroxyethylcellulose 296 hydroxyprogesterone, permeability constant 358 hydroxypropylmethylcellulose (HPMC) 296 adhesivity 474

ophthalmic formulations 370 sodium chloride dissolution 312 hyoscine adsorption 199

ibuprofen, vapour pressure 41, 42 icestructure 202

identification of drugs, eutectics 30-1 ileum 343

imidazole interactions 411, 412 imides, cyclic 445-6 imipramine excretion 399 immersional wetting 27 immunoglobulin Fc fragment 437 impaction, inertial in aerosol deposition 379

impinger devices 476-7 indometacin, pH effect on solubility

151, 152 infant formula 71-2 Infusaid implantable pump 38-9 infusion fluids 153, 154 inhalation therapy 376-83 devices 377 see also aerosols inorganic materials, solubility in water 149 inositol hydration 147 insolubility 141 insulin 455-8 absorption 353-4 administration 352-5 adsorption 291-2, 293 associated states 442 clearance from i.m. site 349-50 crystallinity modification 352-3 fibril formation 455-6 formulation 455, 456 pH 354, 437

poly(vinyl chloride) interactions

417-18 precipitation 455-6 preparations 455, 456 recombinant human 456-8 self-regulating delivery system

354-5 solubility 354, 437 subcutaneous administration

353-4 see also zinc insulin insulin aspart 455, 456-8 insulin glargine 457-8 insulin lispro 455, 456-8 interactions of drugs 3, 393-4 cation-anion 402-5 molecular complexes 410-14 physical mechanisms 425-9 with plastics 417-19 polyions 405 protein binding 419-25 see also adsorption; chelation; complexation interfacial reactions 314, 316-17 interfacial tension 179, 245 interferon y (IFNy) 443 interleukin 1p 437 internal energy 58 intestinal absorption 335-6

drugs 398-9 intracavernosal injection 389, 390 Intralipid 251, 252

intramuscular administration 349-55

injection site 351 intrathecal route 389-90 intravenous containers 417-19 intravenous therapy 405 iodine solubilisation 226

solubility 300 iodophors 226, 300 ion-exchange resins 307-10

interactions 413-14 ionic parameters, mean 64 ionic product of water 79 ionic species hydration 147-8 ionic strength, drug stability 120-2 ionisable species partitioning 165-6 ionisation drugs in solution 75-89 percentage calculation 80 polyprotic drugs 83 water 79

weakly acidic/basic drugs 77 ionisation constant 77, 78-9, 79-80, 82

ionised drugs activity 63 solubility 150-5 ion-pair formation 340-1, 405 iontophoretic drug-delivery system

363, 364, 365 iron sequestering 410 iron-dextran complexes 300 isobutanol 166 isoelectric point 83, 437, 439 isoflurane, blood/gas partition coefficient 72 isomerisation 98-9

cis-trans 99 isophane insulin 353 isoprenaline, buccal absorption 347 isopropyl myristate, in vitro evaluation 467-8, 470 isotonic solutions 71, 73-5

jejunum 343 jet injectors 365-6

kaolin 416 kaolinite E. coli adhesion 267 flocculation 259 ketoprofen, photodegradation 101 kinetic energy 57-8 kinetics of drug decomposition in solution 102-10 solid dosage forms 110-13

labetolol ionic species distribution 83 structure 84 lamellar phase 210-11 Langmuir constants 196 Langmuir equation 195 Langmuir trough 186 large intestine 344 latex particle aggregation 254-5 laxatives, bulk 290-1 Le Chatelier's principle 46 lectins 266

Leuconostoc mesenteroides 298 levodopa, antacid effects 397 lidocaine intramuscular injection 351 ligands 406

light, effect on drug stability 122,

127, 133 lincomycin 415-16 Lipiphysan 251 Lipofundin 251

lipophilicity (log P) 166, 168-75, 334-5 P blockers 370, 371, 372 biological activity 166 calculation from molecular structures 174 drugs 168

protein binding 420, 422-4 liposomes 214, 215

suspensions 254, 263, 265 liquid crystals 210-14 lyotrophic 210-11 thermotropic 211-14 cholesteric 212, 213-14 nematic 212, 213-14 smectic 212, 213 liquids boiling point 142 gas solubility 46-8, 49 pH 113-18

shear conditions for flow through needle 254 stability 113-23

surface and interfacial tensions 179 loading of drug, effect on release rate 470

log P see lipophilicity (log P) Lowry-Bronsted theory 75-6 lubricants, biological 291 Lundelius' rule 198 luteinizing hormone-releasing hormone (LH-RH) analogues 383

luteinizing hormone-releasing hormone (LH-RH) decapeptide derivative 417 Lyofoam 302 lyophilised proteins 452

macrodissociation constants 83, 85 Macrogols see polyoxyethylene glycols macromolecular compounds ion binding 288 structural formulae 277-8 macromolecules adsorption 291-3 coacervation 314, 315-16 desolvation 315-16 ionic and drug interactions 404-5

magnesium carbonate 398 magnesium oxide 398

mannitol clearance from i.m. site 349-50 hydration 147 jet injectors 366 maximum additive concentration

(MAC) 220-1 M-cells 23, 343 mecamylamine 398 mecillinam hydrolysis 117-18 pH-rate profile 118 meclofenamic acid 412 medazepam 419 mefenamic acid 412 melting point of solids 142 membrane transport 452 membranes, rate-limiting 320-1 meperidine 4

mercaptopurine, extemporaneous suspension 259 methacholine chloride, buccal absorption 347 methenamime mandelate 399-400 methionine 447, 448 methotrexate 389 methyl parabens 419 methylcellulose 291, 295 methylphenylsilicone 310 methyltestosterone, solubility 144, 146

Meyer-Overton hypothesis 48, 166-7 micelles 123 counterions 209 electrolyte addition 209 formation 201-2, 203-4 hydrophobic factor 203 ionic 206, 207 kinetic 207

nonionic 206, 207, 208 reverse 205, 206 size 207-10

solubilisate location 221-2 structure 204-7 micellisation 201-10 miconazole nitrate, oxidation susceptibility 96, 97 microbial cells, adsorption to surfaces 266-7

microcapsules 314-17, 318, 319-20 encapsulation physical methods 317

polyamide 319 preparation processes 314-17 suspensions 254 microcrystals 280

cellulose 303 microdissociation constants 83, 84-5 microemulsions 237, 245-7 formation 247 structure 245-6 microparticles 231 micropatches, vaginal 376

microphase separation 280 microspheres 314-17, 318, 319-20 emulsions 265 polymers 453, 455 protein 319-20 suspensions 254 microvilli 343-4

midazolam, photodegradation 118 milk, human, drug distribution 174-5

milk : plasma (M/P) ratio 174-5 Miller indices 9-10 milliequivalents 56, 57 minimum alveolar concentration

(MAC) 48 minocycline, lipid solubility 168-9 moisture adsorption 124 load 452, 455 solid drug stability 123-7 stability of solid state drugs 133, 134 molality 56

molar enthalpy of vaporisation 40, 41

calculation 43 molar quantity, partial 67 molarity 56

molasses, infected wound treatment

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