Transport Processes in Pharmaceutical Systems (Drugs and the Pharmaceutical Sciences: a Series of Textbooks and Monographs)

DK3131_fm......Page 2
Transport Processes in Pharmaceutical Systems......Page 3
Preface......Page 12
Contributors......Page 16
Contents......Page 14
A. Thermodynamic Basis for Mass Transfer......Page 19
Contents......Page 0
B. The Systems Approach to Mass Transfer Problems......Page 21
II. CONVECTION......Page 23
A. Stirred Tank Models......Page 24
B. Plug Flow Models......Page 26
C. Complex Flows......Page 28
III. DIFFUSION......Page 30
1. Convective Diffusion Approach......Page 33
2. Nonequilibrium Thermodynamics Approach......Page 34
1. Gradients in Electrical Potential......Page 35
2. Combined Heat and Mass Transfer......Page 36
V. SUMMARY......Page 37
VI. GLOSSARY OF TERMS......Page 38
REFERENCES......Page 39
I. INTRODUCTION......Page 41
A. Fick’s First Law......Page 42
B. Fick\'s Second Law......Page 43
III. CONVECTION AND GENERALIZED MASS BALANCE EQUATIONS......Page 45
A. Steady Diffusion Across a Thin Film......Page 47
B. Steady Diffusion Across a Membrane......Page 49
C. Steady Diffusion Across a Membrane with Aqueous Diffusion Layers......Page 51
D. Steady Diffusion in Parallel......Page 54
E. Unsteady Diffusion into a Semi- Infinite Membrane......Page 55
F. Unsteady Diffusion Across a Membrane......Page 59
G. Effect of Reaction on Membrane Diffusion......Page 61
V. DIFFUSION IN A CYLINDER......Page 63
VI. DISSOLUTION OF A SPHERE......Page 65
VII. INTRINSIC DISSOLUTION......Page 67
REFERENCES......Page 70
A. Compartmental Models......Page 72
B. Physiologically Based Pharmacokinetic Models......Page 74
A. Compartmental Models......Page 77
B. Physiologically Based Pharmacokinetic Models......Page 81
C. Distributed Parameter Models......Page 90
A. Compartmental Models......Page 91
1. Organ Blood Flows and Volumes......Page 93
2. Partition Coefficients......Page 94
3. Mass Transfer Coefficients......Page 95
4. Clearances......Page 96
6. Miscellaneous......Page 97
8. Model Validation......Page 98
C. Distributed Parameter Models......Page 99
REFERENCES......Page 100
I. INTRODUCTION......Page 104
1. Miscible Phases......Page 105
2. Immiscible Phases......Page 108
1. Miscible Liquid Phases......Page 109
2. Immiscible Liquid Phases......Page 111
2. Immiscible Phases......Page 112
D. Liquid/ Membrane/ Semisolid Interface......Page 113
1. Mass Transfer from Constant Surface Area Solids......Page 114
2. Mass Transfer from Finely Divided Drug Particles......Page 115
F. Liquid/ Cultured Cell Interface......Page 116
A. Diffusion Coefficients......Page 117
B. Mass Transport Quantities......Page 119
V. ERROR ANALYSIS AND METHOD VALIDATION......Page 120
REFERENCES......Page 123
I. INTRODUCTION......Page 126
II. DISSOLUTION OF ACIDIC AND BASIC DRUGS IN UNBUFFERED MEDIA......Page 127
III. DISSOLUTION OF ACIDIC AND BASIC DRUGS INTO BUFFERED SOLUTION......Page 134
IV. DISSOLUTION OF MULTICOMPONENT SOLIDS......Page 136
V. DISSOLUTION OF POORLY SOLUBLE COMPOUNDS IN SURFACTANT SOLUTIONS......Page 141
A. Film Equilibrium Model......Page 142
B. Reaction Plane Model......Page 145
VI. DISSOLUTION OF POORLY SOLUBLE DRUGS IN EMULSION SYSTEMS......Page 146
VII. PARTICLE DISSOLUTION......Page 149
A. Boundary Layer Thickness......Page 150
B. Mathematical Models for Particle Dissolution: Monodisperse Populations......Page 151
C. Mathematical Models for Particle Dissolution: Polydisperse Populations......Page 154
VIII. CONCLUSIONS......Page 156
REFERENCES......Page 158
II. GASTROINTESTINAL EPITHELIA — STRUCTURE AND FUNCTION......Page 164
A. Precellular Barriers......Page 170
B. Lipid Barriers, Transcellular Partition Path, Surface Area......Page 171
C. Paracellular Transport — Equivalent Pore and Circuit Theory......Page 178
D. Membrane Transport Facilitators: Carrier, Channel, and Endosomal Proteins......Page 182
A. Kinetics of Cellular Diffusion......Page 183
B. Active and Facilitated Transport......Page 184
C. Mediated Transport Kinetics: Saturation and Inhibitors......Page 185
D. Exchange Phenomena: Cis and Trans Effects......Page 187
A. Ion Gradients: Solute – Solute Coupling......Page 189
B. Osmotic Gradients: Solute – Solvent Coupling......Page 191
D. The Role of Metabolism and Intestinal Secretion: Reaction – Transport Coupling......Page 192
VI. TRANSPORT ADAPTATION AND REGULATION......Page 193
VII. ISOLATED EXPERIMENTAL METHODS OF STUDY AND CORRELATIONS WITH IN VIVO ABSORPTION......Page 194
VIII. SUMMARY......Page 196
REFERENCES......Page 197
A. Introduction......Page 202
B. Ester Derivatives as Prodrugs......Page 203
C. Oral Prodrugs for NEH Acidic Compounds......Page 208
D. Prodrugs for Amines......Page 210
E. Enzyme Prodrugs Targeting Specific Enzymes......Page 212
F. Amino Acid or Peptidyl Derivatives as Prodrugs......Page 213
A. Introduction......Page 219
C. The Michaelis – Menten Equation......Page 220
D. Enzymes in General......Page 222
1. The Luminal and Mucosal Cell Enzymes......Page 223
F. Intestinal Mucosal Peptidases......Page 224
A. Introduction......Page 227
B. Modeling Prodrugs and a Targeted Drug Delivery System......Page 228
REFERENCES......Page 230
I. INTRODUCTION......Page 236
A. General Background on Passive Transport......Page 237
B. Selection of a Transport System and Parameters to Consider......Page 242
A. Steady-State Kinetics Under Sink Conditions......Page 250
B. Steady- State Kinetics Under Non- Sink Conditions......Page 253
C. Permeability Coefficients......Page 255
A. Morphology of the Paracellular Route......Page 256
1. Molecular Restricted Diffusion Within an Electrostatic Field of Force......Page 259
2. Barriers in Series: Tight Junction and Lateral Space......Page 262
1. Hydrophilic Extracellular Permeants......Page 263
2. Pore Size Changes and Pharmacological Perturbation......Page 268
3. Barrier Assessment of the Tight Junction and Lateral Space......Page 271
4. Correlation of Paracellular Permeability with Transmonolayer Electrical Resistance......Page 275
A. Permeability Coefficient......Page 278
B. Applications......Page 280
A. Permeability Coefficients......Page 281
1. Steroids......Page 283
2. Peptides......Page 291
3. Influence of the Perturbed Paracellular Route......Page 294
A. Permeability Coefficients......Page 296
B. Application......Page 298
A. Biophysical Model Description......Page 305
B. Interrelation of Fluxes and Extent of Metabolism......Page 308
C. Donor Disappearance and Receiver Appearance Kinetics......Page 309
D. Applications......Page 311
A. Introduction......Page 314
B. Influx Kinetics and the Apical Membrane Domain......Page 317
C. Efflux Kinetics from the Apical Membrane Domain......Page 321
D. Biophysical Model for Transcellular Flux Kinetics......Page 324
IX. USE OF IN VITRO MONOLAYER STUDIES TO PREDICT RESULTS IN VIVO......Page 326
REFERENCES......Page 330
I. INTRODUCTION......Page 334
1. Cornea......Page 336
2. Conjunctiva......Page 337
B. Electrophysiology......Page 338
III. PERMEABILITY BARRIERS IN THE CORNEA AND THE CONJUNCTIVA......Page 358
A. Conventional Means......Page 362
1. Activation of Ion-Dependent Cotransport Processes......Page 367
2. Modulation of Extra- and Intracellular Ca2  Levels......Page 369
4. Modulation of Cl  Channels......Page 371
REFERENCES......Page 376
I. INTRODUCTION......Page 392
A. pH-Partition Hypothesis......Page 393
B. Absorption Potential Concept......Page 395
A. Macroscopic Mass Balance Approach......Page 396
B. Microscopic Mass Balance Approach......Page 403
A. Dispersion Model......Page 406
B. Mixing Tank Model......Page 408
C. Compartmental Absorption and Transit Model......Page 410
V. SUMMARY......Page 417
VI. NOTATION......Page 418
REFERENCES......Page 419
I. INTRODUCTION......Page 425
II. FUNDAMENTAL CONCEPTS......Page 426
A. One-Compartment Systems......Page 429
B. Two- Compartment Systems......Page 447
C. Pulsatile Systems......Page 453
REFERENCES......Page 455
I. INTRODUCTION......Page 459
A. Frames of Reference......Page 460
B. Diffusion Coefficients......Page 461
C. Fickian Sorption......Page 462
D. Fickian Permeation......Page 463
III. DIFFUSION IN POLYMER – PENETRANT SYSTEMS......Page 465
A. Free Volume Theories......Page 466
B. Glassy State and Anomalous Diffusion......Page 471
A. Swelling and Case II Transport......Page 474
B. Diffusion in Swollen Gels......Page 475
REFERENCES......Page 481
I. INTRODUCTION......Page 486
A. Monomer Polymerization......Page 489
1. Types of Gels......Page 498
2. Chemical Cross-Linking......Page 501
3. Radiation Cross-Linking......Page 502
4. Physical Cross-Linking......Page 503
C. Other Techniques for Hydrogel Synthesis......Page 505
A. Equilibrium Swelling Degree......Page 506
B. Swelling Kinetics......Page 521
C. Hydrogel Permeability......Page 532
1. Biocompatibility......Page 541
2. Biodegradability......Page 543
IV. SUMMARY......Page 545
REFERENCES......Page 546
II. pH- MODULATED SYSTEMS......Page 560
III. PHOTOSENSITIVE POLYMERIC MEMBRANES......Page 565
IV. TEMPERATURE- SENSITIVE HYDROGELS......Page 569
V. ELECTRIC CURRENT – SENSITIVE POLYMERS......Page 578
REFERENCES......Page 584
I. INTRODUCTION......Page 587
II. CRYSTALLINITY AND AMORPHOUS MATERIALS......Page 588
III. PHASE TRANSITIONS......Page 599
C. Dielectric Analysis......Page 602
IV. POLYMORPHISM......Page 603
V. HYDRATION......Page 611
VI. CONCLUSIONS......Page 618
REFERENCES......Page 619
I. OVERVIEW OF THE FREEZE- DRYING PROCESS......Page 623
A. Mass Transfer and Resistance......Page 626
B. Heat Transfer Coefficients and Temperature Differences......Page 629
C. Coupling Between Heat and Mass Transfer: Process Control......Page 631
A. Kinetic Theory, Collisions, and Gas Pressure......Page 636
B. Distribution of Velocity: The Maxwell – Boltzmann Distribution......Page 638
C. Calculation of Average Quantities for a Gas......Page 643
1. The Intensity Equation......Page 645
2. The Knudsen Cosine Law......Page 648
E. Mean Free Path......Page 649
F. Flow Through an Orifice: Knudsen Effusion......Page 651
G. Rates of Sublimation and Evaporation......Page 653
H. Viscosity of Gases and Slip Flow......Page 656
1. General Principles......Page 663
2. Free Molecular Flow......Page 664
3. Transition Flow in a Cylindrical Tube......Page 667
1. Gases at High Pressure......Page 671
2. Free Molecular Flow Heat Transfer......Page 674
3. Heat Conductivity in Transition Flow......Page 677
A. Blackbody Radiation......Page 679
B. Real Surfaces......Page 681
2. Resistance of Dried Product......Page 684
1. Special Cases of Radiative Heat Transfer in Freeze Drying......Page 690
2. Mechanisms of Heat Transfer in Freeze Drying......Page 693
3. Variations in Heat Transfer......Page 694
ADDITIONAL REFERENCES......Page 698
A. Hygroscopic Materials......Page 699
B. Empirical Approaches to Moisture Uptake......Page 700
II. VAPOR – LIQUID EQUILIBRIA......Page 701
III. HEAT CONDUCTION......Page 703
A. Heat Conduction in Rectangular Coordinates......Page 705
B. Heat Conduction in Spherical Coordinates......Page 707
IV. HEAT TRANSPORT CONTROLLED MOISTURE SORPTION ( PURE WATER ATMOSPHERE)......Page 709
A. Heat Flux Caused by Moisture Uptake in One Dimension......Page 712
B. Heat Transport Limited Moisture Uptake in Spherical Coordinates......Page 713
V. MASS TRANSPORT CONTROLLED MOISTURE SORPTION......Page 715
A. Mass Transport Limited Moisture Uptake in One Dimension......Page 717
VI. COMBINED MASS AND HEAT TRANSPORT CONTROLLED MOISTURE SORPTION......Page 719
VII. DELIQUESCENT MATERIALS IN POROUS SYSTEMS......Page 721
REFERENCES......Page 724