A
Abbreviated new drug application (ANDA), 498–499, 504
Abscopal effect, 553
Absorption, distribution, metabolism, and elimination/excretion (ADME), 451, 496
Acyclovir monophosphate (ACVp), 299
Allergic conjunctivitis (AC), 313
Alza’s Alzamer®, 10
ALZET® osmotic pump, 143, 153–155
ANDA, see Abbreviated new drug application
Andrx™ system, 182
Antibody drug conjugates (ADCs), 117, 496
Assisted model building and energy refinement (AMBER) program, 445
AstraZeneca proprietary compounds, 461
Atrix’s Atrigel®, 10
B
Bacterial-vectored vaccines, 397
Basic local alignment search tool for proteins (BLASTP), 457
BCS, see Biopharmaceutics classification system
Bell’s inequality, 446
Benign prostatic hyperplasia (BPH), 537
Binary kernel discrimination method, 453
BindingDB, 453
Bioadhesion, 318
BioErodible MucoAdhesive Film (BEMA™), 210
Bioisosterism, 450
Biopharmaceutics classification system (BCS), 48–49, 496, 518
BLASTP, see Basic local alignment search tool for proteins
Breast cancer resistance protein, 451–452
Breath Powered™ Bi-Directional™ device, 240–241
Breath Powered™ OptiNose liquid device, 246
Brick dust molecules, 50
Buccal and sublingual drug delivery
aerosol spray, 208
oral mucosa
drug delivery (see Oral transmucosal drug delivery)
epithelial barrier, 204
lining mucosa, 203
local/topical delivery, 207
masticatory mucosa, 203
mucus barrier, 205
physiological characteristics, 203
specialized gustatory (taste) mucosa, 203
transport mechanisms, 206
sublingual tablets, 208
Business-to-business marketing
Big Pharma/Big Biotech, 510
biopharmaceuticals, 512
contract development and manufacturing organizations, 511
contract manufacturers, 512
drug delivery business model, 511
drug delivery companies, 510
drug delivery technology market
current status, 514
marketing, 514
third parties in-license, 514–516
drug delivery technology maturity continuum, 513
joint ventures, 513
merger, acquisition, and spin-out activity, 514
small-to medium-sized pharma, 510
specialty pharma, 510
Bystander effects, 115
C
CAGR, see Compound annual growth rate
Calcium phosphate nanoparticles (CPNPs), 416
Candizole-T® tablet, 297
Carbon nanotubes (CNTs), 111, 416–417
Carraguard gel, 298
Caya Countoured diaphragm, 292
Cell-mediated immune (CMI) response, 391, 396
Center for Drug Evaluation and Research of FDA, 466
BBB
anatomy and physiology, 362–364
function of, 361
disorders of, 362
drug delivery
convection-enhanced delivery, 371
intracerebral implants, 371
intracerebroventricular infusion, 370–371
intranasal administration, 371
natural transport mechanisms, 365–368
nose-to-brain delivery, 365
pharmaceutical approaches, 365
physiological approaches, 365
surgical approaches, 365
Certificate of Compliance/Certificate of Conformance, 469
Cervicovaginal mucus (CVM), 286–287
Cervidil®, 298
Cervovaginal fluid (CVF), 283–284
Cheminformatics
BindingDB, 453
ChEMBL, 452
chemistry space, 454
DrugBank, 453
GlaxoSmithKline, 452
Guide to Pharmacology, 453
NRList BDB, 453
PubChem database, 453
RO5, 452
SwissBioisostere, 453
Chemistry at HARvard Molecular Mechanics (CHARMM) program, 445
Chemistry, manufacturing, and controls (CMC)
nanomedicine drug product
biophysical characterization, 472–474
changes to manufacturing, 476–477
chemical/content specifications, 470–472
CPX-1 characterization, 473
CMC, see Chemistry, manufacturing, and controls
CNS, see Central nervous system
CNTs, see Carbon nanotubes
Code of Federal Regulations (CFR), 466
Combined oral contraceptives (COC), 300
Comparative molecular field analysis (CoMFA), 454–455
Comparative molecular similarity indices analysis (CoMSIA), 455
Composition–structure–property (CSP), 539
Compound annual growth rate (CAGR), 483, 492, 518
Computational chemistry
computational quantum chemistry, 444
computational quantum mechanics
Bell’s inequality, 446
chlorotrifluoromethane, 446–447
Coulomb’s law, 447
electron–correlation methods, 448
halogen bonds, 446
Hamiltonian operator, 447
Hartree–Fock method, 448
Laplacian operator, 448
linear combination of atomic orbitals, 448
DFT, 444
enzyme–substrate interactions, 444
molecular dynamics simulations, 445–446
Conceptrol®, 296
Condensation polymerization, 337
Consumer markets
place, 488
Controlled-release drug delivery
description, 28
diffusion control, 29
dissolution control, 29
glucose-sensitive transient insulin delivery device, 596
ion-exchange control, 29
matrix diffusion systems, 45
osmotic pressure-activated CR systems, 42–44
osmotic pressure control, 29
pellets, 2
rate-controlling membrane
Hydron®, 6
Implanon®, 6
TTS, 44
vaginal rings, 6
Vantas®, 6
Convection-enhanced delivery (CED), 371
“Copper T,” 291
CPX-351, 474
Critical process parameters (CPP), 475
Critical quality attributes (CQA), 475
Cross-disciplinary collaboration, 599
Cypher® stent, 12
Cytomegalovirus retinitis (CMVR), 151, 313
D
Delayed release coatings, 2
Delayed release (DR) delivery systems
description, 28
enteric coating, 33
plasma concentration–time profile, 27
Density functional theory (DFT), 444, 448
Depo-Provera®, 294
DES, see Drug-eluting stents
Dissolution-controlled SR delivery systems
matrix dissolution systems, 36
reservoir dissolution systems, 36
Donnan effect, 343
Dopamine active transporter (DAT), 451
Dox-containing LTSL (Dox-LTSL) formulation, 549–550
Doxorubicin (Dox)
anthracycline antibiotic, 530
bright-field image, 533
cell’s electron transport chain, 531
intravenous dosing, 531
metastatic breast cancer, 535
neoplastic agent, 531
non-PEGylated liposomal, 532
ovarian cancer, 535
PEGylated polymer design, 533
structure and mechanism of action, 531
vascular and interstitial liposome, 533–534
DPIs, see Dry powder inhalers
Drug-coated balloon (DCB), 13
Drug dapivirine (DPV), 292
Drug-eluting, bioresorbable stents (DEBS), 13
Drug-eluting stents (DES), 12–13, 157
Drug master file (DMF), 469
Drug solubility, 50–51, 86, 146, 255, 460–461
asthma and COPD, 266
dual-drug products, 267
jet-milled drug, 267
multi-unit dose devices, 268–269
pulmonary bacterial infection, 266
unit-dose devices and capsules, 268
Duke Hyperthermia Program, 529
DuraSite®, 319
DUROS® implantable osmotic system, 155–156
E
Electrospun fibers, 299
EMA, see European Medicines Agency
Emergency contraception (EC), 291
Endometrin®, 298
Enhanced permeability and retention (EPR) effect, 14–15, 111, 113–114, 588–589
Enteric-coating polymers, 2, 187–188
Epithelial barriers
access barriers, 594
barrier properties regulation, 76
efflux pumps, 89
female reproductive tract, 97
hydrophilic molecules, 594
keratin, 88
micro-and nanoparticulate DDS, 595
mucus, 89
physicochemical properties
aqueous solubility, 86
chemical stability, 87
lipid solubility, 83
Lipinski’s rule of five, 87
molecular volume, 86
molecular weight, 86
partition coefficient, 83
respiratory tract
primary function, 94
trachea and bronchioles, 95–96
strategies for, 595
transcellular pathway
sink conditions, 80
transcytosis pathways
phagocytosis, 82
pinocytosis, 82
EPR effect, see Enhanced permeability and retention effect
Essure® system, 289
Ethinyl estradiol (EE), 285
European Medicines Agency (EMA), 161, 466–467, 507, 564–565, 592
Extended drug release, see Sustained release delivery systems
EyeGate® II Delivery System, 327
F
Fast release delivery systems, see Immediate release delivery systems
Female reproductive tract (FRT)
anatomy and physiology
cervix, 282
fallopian tubes, 282
gonadal differentiation, 281
Müllerian epithelium, 281
uterus, 282
antibody delivery, 299
COCs, 300
contraception, 288
electrospun fiber mats, 299
FRT infections, 288
HIV, topical preexposure prophylaxis, 288–289
HPV vaccination, 300
HSV-2, 300
in vivo and ex vivo models
EpiVaginal™ tissues, 302
mice, 302
nonhuman primates, 301
rabbit, 301
sheep, 302
vaginal mucosa, 302
lower FRT, drug delivery
cervix and combination barrier devices, 292
erodible vaginal solids, 297
toxins, vaginal absorption of, 292
vaginal inserts, 298
menopausal symptoms, 288
mucus-penetrating particles, 299
multipurpose prevention technologies, 298
oral PrEP, 300
PCOS, 300
permeability enhancers and enzymatic inhibitors, 300
semen-triggered systems, 299–300
small-interfering RNAs and gene silencing, 299
systemic delivery, 287
upper FRT, drug delivery
fallopian tubes, 289
intrauterine drug delivery, 289–291
ovaries, 289
user/patient interventions, reduction/elimination of, 287
vaginal physiology
compartments of, drug transport, 284–286
drug properties, 286
pharmacokinetic models, 286
pregnancy, 287
FemCap™, 292
Fertiring®, 294
Fine particle fraction (FPF), 257
Fit-lizer™ multidose system, 239
Flux-controlled pump (FCP), 293
Franklin–Watson–Crick structure, 454
FRT, see Female reproductive tract
Fumaryl diketopiperazine (FDKP), 269
G
Gastro-retentive SR delivery systems, 42
Gene delivery systems
disease-specific expression systems
cancer, 386
diabetes, 387
myocardial infarction, 387
neuronal diseases, 387
DNA-based gene therapy, 376
intracellular organelle-targeting gene delivery systems
mitochondria targeting, 386
nuclear-targeted gene delivery systems, 384–386
plasmid expression vector, 377–378
polymerase chain reaction, 378–379
polymer-based delivery systems
bioreducible polymers, 380–381
cytoplasm-sensitive reducible polymers, 380
poly(amido ethylenimine), 381–382
poly(disulfide amine), 382–383
proton-buffering effect, 380
RPC, 383
virus-based delivery systems, 384
protein drugs, 375
recombinant DNA technology, 376–377
scheme of, 376
viral vector, 380
Geomatrix™ system, 180
Geometric standard deviation (GSD), 258
Giant unilamellar vesicles (GUVs)
acyl solid–liquid phase transition, 539, 541
adhesive and repulsive interactions, 539, 545
DMPC phase transition work, 541–542
elastic expansion and failure of membranes, 539–540
gel-phase vesicle, 542
lipid vesicles, 546
molecular exchange with lysolipids, 539, 543–544
properties of, 539
SOPC/POPC-mixed system, 541–542
two-molecule-thick membrane, 546
yield shear and shear viscosity, solid membranes, 539, 542–543
GlaxoSmithKline, 452
Gold nanoparticles (AuNPs), 412–413
Good laboratory practices (GLPs), 467
Good manufacturing practices (GMP), 467
G protein-coupled receptors (GPCR SARfari), 452
Grease ball molecules, 49–50, 66
Guide to Pharmacology, 453
GUVs, see Giant unilamellar vesicles
GyneFix®, 291
Gynol®, 296
H
Hand–foot syndrome, 535
Hartree–Fock method, 448
Health technology assessment (HTA), 491, 505, 508, 518
Henderson–Hasselbalch equation, 85
Hepatocellular carcinoma study, 564–569
HercepTest®, 409
Herceptin®, 409
Herpes simplex virus (HSV), 296
High-throughput screening (HTS), 48, 450
HTA, see Health technology assessment
Human intestinal peptide transporter (hPEPT1), 451
Hybrid products, 499
Hydrogels
biodegradability, 345
chain-growth/addition polymerization, 338–339
chemically cross-linked networks, 340–341
cross-linked polymer chains, 333–334
degree of swelling and shrinking, 334
diffusivity, 344
Donnan effect, 343
glass transition temperature, 345
glassy polymer network, 345
like liquids, 333
like solids, 333
linear polymers, 340
long-chain biopolymers, 336
membrane vs. monolith, 342–343
natural hydrogels, 336
partition and diffusion coefficients, 343
permeability, 343
physically cross-linked networks, 336, 341–342
role of, 342
solubility, 344
steady-state flux, 342
step-growth polymerization, 336–337
stimulus-sensitive hydrogels
antigen-responsive reversible swelling, 351
closed loop/self-regulated systems, 347
degree of swelling determination, 345–347
external stimulus-sensitive systems, 353–355
glucose-sensitive systems, 349–351
imprinted hydrogels, 347
multiresponsive systems, 355–356
open-loop systems, 347
temperature-sensitive systems, 347–348
Hydron®, 6
Hydrophilic swellable matrix systems, 41, 177–179
Hydrophobic matrices, 179
I
Immediate release (IR) delivery systems
drug dissolution rates and solubility, 30–31
drug membrane permeability, 29–30
liquid dosage forms, 29
plasma concentration–time profile, 26–27
solid dosage form, 30
compressed steroid pellets, 141–142, 151
drug-eluting stents, 157
DUROS®, 143
emerging technologies, 157–158
erodible implants, 152
examples, 140
Folkman experiments, 142
host response/biocompatibility, 160–161
Implanon® system, 152
manufacturing, 162
Ocusert®, 143
osmotic pumps
delivery rate, 153
DUROS® implantable osmotic system, 155–156
Progestasert®, 143
shelf life, 162
sterilization/aseptic processing, 162
target product profile, 158–159
treatment biology, 159
Vitrasert® implant, 151
Imprinted hydrogels, 347
Inhalation aerosol therapy, 250
Innovation Task Force, 467
Inorganic-nanosized theranostics
CPNPs, 416
mesoporous silica nanoparticles, 415–416
quantum dots theranostics, 414–415
In situ gelling system, 319
IntelliCap® system, 183
International Nonproprietary Name (INN), 116, 452
International Union of Basic and Clinical Pharmacology/British Pharmacological society, 453
International Union of Pure and Applied Chemistry (IUPAC), 449
Intracellular organelle-targeting gene delivery systems
mitochondria targeting, 386
nuclear-targeted gene delivery systems, 384–386
Intracerebroventricular infusion, 370–371
Intranasal vaccination delivery, 401–402
Intrapulmonary vaccination delivery, 402–403
Intrauterine devices/systems (IUD/IUS), 287, 289–291
clinical history, 294
features, 300
MPT, 298
technical description of, 292–293
IR delivery systems, see Immediate release delivery systems
Iron oxide nanoparticles (IONPs), 413–414
J
Journal of Controlled Release (JCR), 599
K
Kinase SARfari, 452
Kohn–Sham equations, 448
L
Label-sparse quantification method, 457
Lacrisert®, 319
LAIs, see Long-acting injections
Lamina propria, 283
Lauriad™ technology, 207
Lipid membrane mechanochemistry
giant unilamellar vesicle experiments
acyl solid–liquid phase transition, 539, 541
adhesive and repulsive interactions, 539, 545
DMPC phase transition work, 541–542
elastic expansion and failure of membranes, 539–540
gel-phase vesicle, 542
lipid vesicles, 546
molecular exchange with lysolipids, 539, 543–544
properties of, 539
SOPC/POPC-mixed system, 541–542
two-molecule-thick membrane, 546
yield shear and shear viscosity, solid membranes, 539, 542–543
red blood cells, 538
Lipinski’s rule of five (RO5), 452
Liquid OROS (L-Oros®) system, 181–182
Long-acting injections (LAIs), 9–10
emerging technologies, 157–158
examples, 140
Higuchi model, 142
host response/biocompatibility, 160–161
in situ forming systems
Alzamer® Depot™ technology, 144–145
Atrigel®, 144
CLOUD® injectable depot, 146
SABER® depot technology, 145–146
long-acting nanoparticles, 150–151
manufacturing, 162
oil-based (lipophilic) depots, 143–144
OROS®, 143
pegylated peptides/proteins, 146–148
poly(lactide-co-glycolides) (PLGA) systems
in vivo hydrolysis, 142
manufacturing process, 148
microsphere commercial products, 148–149
shelf life, 162
sterilization/aseptic processing, 162
target product profile, 158–159
treatment biology, 159
Low-temperature-sensitive liposome (LTSL), see ThermoDox®
M
MAb, see Monoclonal antibodies
Macromed’s ReGel®, 10
MacroModel, 445
Marketed nasal antimigraine drugs, 230
Marketing
bargaining power of purchasers, 517
bargaining power of suppliers, 517
BCS, 518
brand awareness and loyalty, 518
brands, branding, and brand image, 518
business-to-business market, 510–517
CAGR, 518
cost of capital, 518
data exclusivity, 518
detailing, 518
drug delivery market
definition, 491
drug product exclusivity, 519
effectiveness vs. efficacy, 518
GDP, 518
HTA, 518
hybrid product, 518
marketing/distribution channel, 518
market share, 519
Paragraph IV Patent Certification, 519
payer, 519
pharmaceuticals market
convenience and safety, 501
generic competition, 504
health-care cost control, 505–506
increasing delivery challenges, 500–501
market size and growth, 483–484
obesity and sedentary lifestyles, 502
orphan drug regulations, 504
pediatric regulations, 504–505
personalized medicine, 503
pharmerging markets, 506
weak development pipelines, 504
pharmacoeconomics, 519
pharmacy benefit manager, 519
product adoption and differentiation, 519
product development and product life-cycle management, 519
ADCs, 496
ADME properties, 496
formulations and dosage forms, 497
indications, 497
OTC switches, 497
patents and associated patent-term extensions, 498
pipeline and balance risk, 500
product differentiation, 496–497
technical and investment barriers, 500
product portfolio, 519
product positioning, 519
product, price, place, and promotion, 519
retail cost of medicine, 520
segment and segmentation, 520
successful drug delivery products, 495
active therapeutic moiety, 506
competing products, 507
efficacy and side effects, 507
patent protection and uniqueness of, 509
price and benefits, 508
product launch, 509
products meet market needs, 507–508
types of market needs, 493–494
value-based pricing, 520
Mass median aerodynamic diameter (MMAD), 257–258
Matrix diffusion systems
bioerodible matrix systems, 41
controlled-release systems, 45
homogeneous matrix systems, 39–40
hydrophilic swellable matrix systems, 41
porous matrix systems, 40
Maximum tolerated dose (MTD), 536, 561
Medicated chewing gum, 211
Membrane-controlled drug delivery systems, 4
Merck molecular force field (MMFF), 445
Metered-dose spray pumps, 236–238
Micro-and nanoparticulate DDS, 193–194, 244, 320–321
Microelectromechanical systems (MEMS) technology, 327, 357
Microelectronic controlled release system, 182–183
Microfluidic chips, 357
Micronization, 52
Microprojection arrays (MPAs), 225
Microsyneresis, 340
Modified live vaccines (MLVs), 395
Modified release (MR) delivery systems
description, 27
plasma concentration–time profile, 27
Molecular dynamics (MD) simulations, 445–446
Monoclonal antibodies (MAb), 115–117, 230, 365, 409, 500–501, 503, 589
Mononuclear phagocyte systems (MPS), 109, 111, 113, 122
MR delivery systems, see Modified release delivery systems
Mucoadhesives DDS, 13
Multidrug DDS, 597
Multidrug resistance protein 1 (MRP1), 451
Multipurpose prevention technologies (MPT), 298
N
Nanofabrication techniques
atomic force microscopy, 429
micro-and nanotopography
gecko-inspired nanotopography, 435–436
mucoadhesion, 433
nanowire-coated particles, 432–433
unidirectional drug release, 434
nanochannels
in cell encapsulation, 438
in membrane-controlled drug delivery devices, 436–437
scanning electron microscopy, 429–430
top-down process
solvent casting, 426
Nanomedicines
preclinical safety studies, 467–468
Nanoscale DDS
polyplexes and lipoplexes, 17–18
Nanotechnology
drug-targeting systems, 588
future directions for
echoing nature’s own processes, 593
imaging and theranostics, 593
inflammatory disorders, 592
nanocarrier constructs, 591
pharmacokinetics, 592
microparticles, 588
Nanotechnology Task Force, 466
Nasal cavity
drug delivery (see Nasal drug delivery)
mucociliary escalator, 232
nasal epithelium, 232
Breath Powered™ Bi-Directional™ device, 240–241
deposition and clearance, 236
drops, 240
Fit-lizer™ multidose system, 239
formulation factors
buffers, 244
enzyme inhibitors, 244
gel formers, 243
micro-and nanoparticulate DDS, 244
mucoadhesives, 243
solubility enhancers, 244
limiting factors
complex geometry, 234
mucociliary clearance, 234
mucosal sensitivity, 235
nasal cycle, 235
patient acceptability and compliance, 235
small size, nasal cavity, 233
metered-dose spray pumps, 236–238
nasal powder sprayers, 238–239
nose-to-brain drug delivery, 244–246
pMDIs, 238
Rhinocort Turbuhaler®, 239
vaccines, 246
Nasal powder sprayers, 238–239
National Center for Biotechnology Information (NCBI), 457
Natural hydrogels, 336
Natural transport mechanisms, brain endothelium
adsorptive-mediated transcytosis, 368
low-density lipoprotein receptor-related protein 1, 367–368
Nebulizers
FDA-approved products, 262–263
inhalation solutions, 260
liquid aerosols, 260
New chemical entity (NCE), 598
New drug application (NDA), 498–499
New molecular entity (NME), 467–469
New Zealand white rabbit (NZWR) model, 301
Nonhuman primates (NHP), 285, 301
Norplant®, 5–6, 45, 151–152, 280
Nose-to-brain drug delivery, 244–246, 365
Noyes–Whitney equation, 30–31, 36, 51
Nuclear Receptor Ligands and Structures Benchmarking DataBase (NRList BDB), 453
O
ODTs, see Orally disintegrating tablets
Office of Licensing and Ventures (OLV), 574
Ophthalmic drug delivery
anatomy
anterior cavity, 306
choroid, 307
ciliary processes, 307
extraocular muscles, 306
neuroretina, 307
retinal pigment epithelium, 308
sagittal section, 307
uvea/uveal tract, 307
vitreous chamber, 306
contact lenses and cul-de-sac inserts, 320
epithelial permeability barriers, 310–311
eye diseases
age-related macular degeneration, 313–314
cytomegalovirus retinitis, 313
diabetic retinopathy, 314
intraocular infections, 313
uveitis, 313
FOTE delivery and reproducibility, 317
intravitreal delivery, 314–315
intravitreal implant
anti-inflammatory corticosteroids, 325
fluocinolone acetonide, 325
Iluvien®, 325
nonbiodegradable implants, 325
PRINT™, 325
Vitrasert® implant, 324
intravitreal injection
drug loss, 322
long-acting intravitreal injections, 324
risk factor, 322
iontophoresis and electroporation, 326–327
MEMS technology, 327
micro and nanoparticulate drug delivery systems, 320–321
nasolacrimal drainage, 309
NSAIDs and corticosteroids, 316
physical barriers
sclera, 311
vitreous humor, 312
rapid reflex blinking, 310
suspensions, 318
tear film, 309
topical delivery, 314
transscleral injections, 326
transscleral route, 315
visibility requirements, 308–309
Optimized potential for liquid simulations (OPLS), 445
Oral cavity-targeted vaccines, 405
Oral controlled release, 10–11, 172
Oral drug delivery
advantages, 174
bioavailability
chemical conjugation approaches, 194–195
enzyme inhibitors, 192
micro-and nanoparticulate drug delivery systems, 193–194
mucoadhesives and mucolytics, 192–193
solubility enhancers, 192
systemic delivery via colon, 195
controlled release system
Geomatrix™ system, 180
hydrophilic swellable matrix systems, 177–179
hydrophobic matrices, 179
microelectronic controlled release, 182–183
reservoir drug delivery systems, 180–181
gastrointestinal tract
food constituents, 176
intestinal transit time, 176
mucus barrier, 176
nonabsorbable complex, 176
P-glycoprotein efflux pump, 176
pH range, 176
regional drug targeting, 184–190
Orally active osmotic pumps, 181–182
Orally disintegrating tablets (ODTs), 31–32, 202
Oral transmucosal drug delivery
Actiq® unit, 211
advantages, 201
buccal drug delivery
in vitro and in vivo assessment, 212
lozenge-on-a-stick unit, 211
medicated chewing gum, 211
Nicotrol® inhaler, 211
ODTs, 202
pediatric transmucosal formulations, 212
sublingual drug delivery, 208
vaccine delivery, 205
Organic-nanosized theranostics
multifunctional polymeric micelles, 420
polymersomes, 419
Oros-Concerta®, 181
OROS® platform, 143
Orphan drugs, 484, 498–499, 502, 504
Osmotic pumps
delivery rate, 153
DUROS® implantable osmotic system, 155–156
P
Palmar–plantar erythrodysesthesia (PPE), 535
Palmitoyl-oleoyl-phosphatidylcholine (POPC), 472, 475
Paragard®, 291
Parenteral DDTS
carrier systems
affecting factors, 132
degree of body compartmentalization, 107
particulate carrier systems, 106, 119–131
pharmaceutical aspects, 129–131
pharmaceutical challenges, 132–133
point of injection to site of action route, 131
soluble macromolecular carriers, 106, 115–119
stimulus-sensitive systems, 106–107
stochastic process, 106
drug/therapeutic agent, 105–106
i.v.-administered drug, 104
limitations, 104
pharmacokinetic considerations, 105
prolonged release profiles, 105
Particulate carrier systems
advantages, 119
characteristics, 107
limitation, 119
lipoprotein carriers, 125
liposomes
bilayer composition, 122
conventional liposomes, 122–123
definition, 120
diameters, 121
long-circulating liposomes, 123
multilamellar structures, 121
pharmaceutical liposomes, 122
schematic illustration, 121
niosomes, 124
polymeric micro-and nanoparticles, 125–127
schematic illustration, 107–108
Pathogen-associated molecular patterns (PAMPs), 390–391
PDT, see Photodynamic therapy
Peptide drugs, 156, 233, 235, 496, 501
Permeability glycoprotein (P-gp), 451
Personalized medicine, 503, 597
Pewter tank inhaler, 250
Pharmaceutical Research and Manufacturers of America (PhRMA), 489
Pharmaceuticals market
vs. consumer markets
place, 488
market size and growth, 483–484
Pharmacoeconomic analysis, 490
Pharmacophore
benefits of, 450
computer-aided drug design tool, 450
definition of, 449
HTS, 450
MOLPAT software, 450
SAR analyses, 450
toxophore, 449
2D substructure, 451
Pharma embraces open source models, 577
Pharmerging markets, 506
Photodynamic therapy (PDT), 316, 420–421
Piloplex, 321
pMDIs, see Pressurized metered-dose inhalers
Poly(styrene-4-sulfonate) (PSS), 300
Poly(vinyl alcohol) (PVA), 297
Polycystic ovary syndrome (PCOS), 300–301
Poly(N-(2-hydroxypropyl)methacrylamide) (HPMA) derivatives, 118
Polydimethylsiloxane (PDMS), 291
Polyethylene terephthalate (PET) fibers, 289
Polymer-based delivery systems
bioreducible polymers, 380–381
cytoplasm-sensitive reducible polymers, 380
poly(amido ethylenimine), 381–382
poly(disulfide amine), 382–383
proton-buffering effect, 380
RPC, 383
virus-based delivery systems, 384
Polymeric nanoparticles, 125–126, 150, 190, 419–420
Polymeric soluble carriers
drug-lipid conjugates, 119–120
HPMA derivatives, 118
macromolecular site-specific delivery system, 118
SMANCS, 119
Poly(ethylene-co-vinyl acetate) (EVA) rate-controlling membrane, 5–6
Post-Hartree–Fock calculations, 448
Precision medicines, 597
Preexposure prophylaxis (PrEP), 288–289
Pressurized metered-dose inhalers (pMDIs)
asthma and COPD, 263
CFC propellants, 263
cold Freon effect, 256
FDA-approved products, 266–267
HFA propellants, 263
nasal drug delivery, 238
packaging hardware, 264
PulmoSpheres®, 266
Primary open-angle glaucoma (POAG), 313
Prochieve®, 296
Progering®, 294
Prolieve® thermodilatation system, 537, 555–556
Prolonged drug release, see Sustained release delivery systems
Proteomics
DrugBank and ChEMBL, 457
Kyoto Encyclopedia of Genes and Genomes, 459
label-sparse quantification method, 457
network-based drug repurposing, 458
open-source software SparseQuant, 457
pharmacophore-based method, 457
Search Tool for Interactions of Chemicals, 459
SMILES strings, 459
SynSysNet, 459
target-based drug repurposing approach, 457–458
TARGETgene, 459
tyrosine kinase inhibitors, 458–459
untargeted LS–MS/MS method, 456–457
PubChem database, 453
Pulmonary drug delivery
aerosol treatment, 250
alveolar clearance, 255
cystic fibrosis, 250
destructive and nondestructive mucolytics, 250
dual-drug combination inhalation, 250
endotracheal instillation, 259–260
enzymatic activity, 255
epithelial barrier, 255
mucus and mucociliary clearance, 254
nebulizers
FDA-approved products, 262–263
inhalation solutions, 260
liquid aerosols, 260
particle deposition
aerodynamic particle size, 257
aerosol dispersion performance, 257–258
aerosol velocity, 257
drug properties, 258
inertial impaction, 256
pathological factors, 259
physiological factors, 258
sedimentation, 256
patient acceptability and compliance, 256
pMDIs
asthma and COPD, 263
CFC propellants, 263
FDA-approved products, 266–267
HFA propellants, 263
packaging hardware, 264
PulmoSpheres®, 266
pulmonary nanomedicine, 271
respiratory disorders, treatment of, 250
respiratory tract
bronchial tree, branching of, 251
mucus and mucociliary escalator, 252
respiratory epithelium, 252–253
soft mist inhalers, 270
vaccination, 272
variability, 255
Pulmonary nanomedicine, 271–272
PulmoSpheres®, 266
Q
QikProp program, 461
QSAR, see Quantitative SAR
Quality by design (QbD), 475–476
Quality management system (Q10), 475
Quality risk management (Q9), 475
drug transporters, 455
Franklin–Watson–Crick structure, 454
Hansch method, 454
R
Rabbit vaginal irritation test, 301
Radio-frequency ablation (RFA), 528, 561, 563–569
Receptor-mediated endocytosis (RME), 82–83
Receptor-mediated transcytosis (RMT), 364–365, 367, 593
Recombinant vaccines, 395, 397
Recurrent chest wall (RCW) cancer, 557–561
Reductively degradable polycation (RPC), 383
Regional drug targeting
for small intestinal delivery, 187–188
for stomach
floating drug delivery systems, 185–186
gastroretentive intraruminal devices, 187
high-density systems, 187
magnetic systems, 187
size-increasing delivery systems, 186
Reservoir drug delivery systems, 180–181
Respiratory distress syndrome (RDS), 259–260
Reticuloendothelial system (RES), 109, 356, 369, 386, 411, 525, 589
Retinal pigment epithelium (RPE), 308, 311
Retisert®, 325
RFA, see Radio-frequency ablation
Rhinocort Turbuhaler®, 239
RMT, see Receptor-mediated transcytosis
RO5, see Lipinski’s rule of five
S
Saliva washout concept, 204
Salt screening process, 30
Scientific Advice Working Party, 467
Self-microemulsifying drug delivery systems (SMEDDS), 67–68
Semisolid dosage forms (SSDFs), 207
Sexually transmitted infection (STI), 287
Sildenafil (Viagra®), 297
Simian immunodeficiency virus (SIV), 301
Simplified molecular-input line-entry system (SMILES), 453–454, 459
Skin
anatomy and physiology, 216–217
drug delivery (see Transdermal drug delivery)
SMANCS systems, see Styrene-maleic-anhydride-neocarzinostatin systems
SMILES, see Simplified molecular-input line-entry system
SMILES fingerprint (SMIfp) method, 454
Soft-pattern molding/soft lithography, 428
Soluble macromolecular carriers
advantage, 115
antibodies and soluble synthetic polymers, 107
disadvantages, 115
monoclonal antibodies, 115–117
schematic illustration, 107–108
Solvent accessible surface area (SASA), 461
Solvent casting, 426, 428, 437
Spansule® delivery system, 3–4, 177
SR delivery systems, see Sustained release delivery systems
Steric stabilization process, 53, 113, 369–370, 414
Stimulus-sensitive hydrogels
antigen-responsive reversible swelling, 351
closed loop/self-regulated systems, 347
degree of swelling determination, 345–347
external stimulus-sensitive systems, 353–355
glucose-sensitive systems, 349–351
imprinted hydrogels, 347
multiresponsive systems, 355–356
open-loop systems, 347
temperature-sensitive systems, 347–348
Stimulus-sensitive release (SSR), 28
Structure-based drug design, 455–456
Structure–activity relationship (SAR) analyses, 450
Styrene-maleic-anhydride-neocarzinostatin (SMANCS) systems, 15–16, 119
Sublingual drug delivery, see Buccal and sublingual drug delivery
Suprachoroidal space (SCS), 315
Sustained release (SR) delivery systems; see also Implants; Long-acting injections (LAIs)
description, 28
dissolution-controlled SR, 35–36
gastro-retentive systems, 42
matrix diffusion systems, 38–41
plasma concentration-time profiles, 26–27, 34–35
reservoir diffusion systems, 36–38
SwissBioisostere, 453
T
Tanimoto similarity method, 453
Targeted drug delivery, 28, 115–119, 596
Tear film, 309
Tenofovir disoproxil fumarate (TDF), 294
Tenofovir (TFV) gel, 292
Theranostic nanoagents
basic principles of, 410
CT, 410
inorganic-nanosized theranostics
CPNPs, 416
mesoporous silica nanoparticles, 415–416
quantum dots theranostics, 414–415
MRI, 410
optical imaging, 411
organic-nanosized theranostics
multifunctional polymeric micelles, 420
polymersomes, 419
in 1995
drug-releasing thermal sensitive liposome, 529–530
lipid membrane mechanochemistry, 538–547
clinical testing
clinical programs, 571
Phase 1 for liver cancer, 561–564
Phase 3 for liver cancer, 564–569
Phase 1 prostate cancer, 555–556
Phase 2 recurrent chest wall cancer, 557–561
early commercialization effort, 527–528
hydrophobic anticancer drugs, 529
LDLR, 575
lipid exchange, membranes generates, 548
open-source pharmaceutics, 576–577
phase 3 human clinical trials, 528
preclinical assessment
drug delivery and release, 551–552
Phase 1 canine trial, 552
3D Quantitative SAR (3D-QSAR) approaches, 452
Timoptic XE®, 319
Today™ sponge, 292
Toxophore, 449
active approaches
iontophoresis, 223
advantages, 217
limiting factors, 217
passive approaches
penetration enhancers, 222
TTS, 221
physical approaches
gene guns, 225
intradermal injections, 224
liquid jet injectors, 224
microneedles, 225
MPAs, 225
viable epidermis and dermis, 219
Transdermal therapeutic system (TTS), 6–7, 44, 221
Transdermal vaccine delivery, 400–401
Trichomoniasis, 288
Truvada®, 300
TTS, see Transdermal therapeutic system
Tumor-microenvironment-on-chip (T-MOC), 598
U
Ultrasonic nebulizer, 262
United States Adopted Name (USAN), 452
Uveitis, 313
V
Vaccines
bacterial-vectored vaccines, 397
CMI response, 391
definition, 389
dendritic cells, 390
MLVs, 395
oral cavity-targeted vaccines, 405
recombinant, 395
routes of administration, 398
transdermal vaccine delivery, 400–401
intrapulmonary vaccination delivery, 402–403
oral vaccine delivery, 403–405
via parenteral routes, 392
implants, 399
virus-vectored vaccines, 396–397
VLPs, 397
Vaginal epithelium, 283
Vaginal intraepithelial neoplasia (VAIN), 296
Vantas®, 6
Vascular endothelial growth factor (VEGF), 311
VersiDoser™, 318
ViaNase®, 239
Vibrent® pulsation nebulizer, 239
Vincristine liposome, 526
Virus-like particles (VLPs), 397
Virus-vectored vaccines, 396–397
Vitravene®, 323
VR, see Intravaginal rings
W
Water solubility
amorphous solid dispersions
oral absorption, 62
physical stability, 60
spring-and parachute concept, 59
theoretical phase diagrams, 60–61
cocrystals, 56
colloidal carriers, 68
nanosizing
bottom-up technologies, 54
in vivo dissolution, 52
nanosuspensions, 52
Ostwald–Freundlich equation, 52
schematic diagram, 51
stabilization, 53
oils and coarse emulsions, 66–67
polymeric micelles, 66
X
Xal-Ease® plastic eyedrop dispenser, 317