PHARMACEUTICAL EXTRUSION TECHNOLOGY

Isaac Ghebre-Selassie, Charles Martin9780824740504, 0-8247-4050-5

The only book to bring together all technical information necessary to develop and market pharmaceutical dosage forms that meet current quality and regulatory requirements. Provides in-depth descriptions and analyses of the key parameters of extruders and extrusion processes—highlighting the applicability of melt extrusion in pharmaceutical drug development and product manufacturing.

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Table of contents :
PHARMACEUTICAL EXTRUSION TECHNOLOGY……Page 1
PREFACE……Page 10
CONTENTS……Page 13
CONTRIBUTORS……Page 15
CONTENTS……Page 0
I. INTRODUCTION……Page 17
II. EXTRUDER DESCRIPTION……Page 18
A. HISTORY……Page 20
B. OPERATING PRINCIPLES……Page 21
C. SINGLE-SCREW AND TWIN-SCREW EXTRUDERS……Page 22
A. BACKGROUND……Page 23
C. INTERMESHING AND NONINTERMESHING……Page 24
D. COUNTERROTATING AND COROTATING TWIN-SCREW EXTRUDERS……Page 25
B. INTERMESHING COUNTERROTATING TWIN-SCREW EXTRUDERS……Page 26
C. INTERMESHING COROTATING TWIN-SCREW EXTRUDERS……Page 29
REFERENCES……Page 33
II. GENERAL CHARACTERISTICS OF VARIOUS EXTRUDERS……Page 35
A. SINGLE-SCREW EXTRUDER……Page 40
B. CO-KNEADER……Page 41
C. HIGH-SPEED TWIN-SCREW EXTRUDERS……Page 42
D. LOW-SPEED, LATE-FUSION TWIN-SCREW EXTRUDERS……Page 44
IV. WHAT IS THE DIFFERENCE BETWEEN A STANDARD AND A GMP EXTRUDER DESIGN?……Page 45
A. CLEAN-IN-PLACE……Page 46
B. COMPLETE DISASSEMBLY/CLEANING OF THE EXTRUDER PROCESS SECTION……Page 47
VII. PHARMACEUTICAL PROCESS EXAMPLES……Page 49
B. COMPOUNDING OF A THERMOPLASTIC URETHATHANE PREMIX……Page 50
E. INCORPORATION OF AN ACTIVE SUBSTANCE AND FLUID INTO A CARRIER MATERIAL……Page 51
F. CONVEYING AND COMPACTION OF A TABLET PREMIX……Page 52
REFERENCES……Page 53
I. INTRODUCTION……Page 54
A. HOPPER……Page 56
B. SOLIDS CONVEYING……Page 60
C. GRAVITY-FED SOLIDS FEED SECTION……Page 61
E. PRESSURE-INDUCED SOLIDS TRANSPORTATION……Page 64
III. MELTING/PUMPING/MIXING/VENTING……Page 69
A. MELTING……Page 70
B. PUMPING……Page 72
C. VENTED EXTRUDERS……Page 73
D. MIXING……Page 74
REFERENCES……Page 82
II. MOST BASIC PROPERTIES……Page 84
III. COMMERCIAL TWIN-SCREW EXTRUDERS……Page 86
IV. TWIN-SCREW ELEMENTS—CLASSICAL AND NOVEL TYPES……Page 87
V. DETERMINING SANITATION THRESHOLD LEVELS……Page 89
VI. GETTING STARTED……Page 91
VII. BASIC SCREW TYPES……Page 92
VIII. MASS-TRANSFER REGIONS……Page 100
IX. MIXING……Page 102
X. SCALE-UP AND SCALE-DOWN……Page 106
XI. UNIT OPERATIONS……Page 108
XII. SCREW AND BARREL DESIGNS FOR TOTAL SYSTEMS……Page 110
XIII. COROTATION OR COUNTERROTATION?……Page 111
XIV. SUMMARY……Page 112
REFERENCES……Page 113
CHAPTER 5: DIE DESIGN……Page 114
I. FLAT DIES……Page 115
II. ANNULAR DIES……Page 118
III. DESIGN CRITERIA……Page 120
V. MANUFACTURING……Page 123
REFERENCES……Page 124
II. PREPARATION OF DRY AND WET INGREDIENTS……Page 125
PROCESS DESCRIPTION……Page 126
AUTOMATIC PREMIX PRODUCTION IN GAIN IN WEIGHT BATCHING MODE……Page 127
AUTOMATIC PREMIX PRODUCTION IN LOSS IN WEIGHT BATCHING MODE……Page 128
AUTOMATIC PREMIX PRODUCTION IN LOSS IN WEIGHT FEEDING MODE……Page 130
GENERAL BENEFITS OF DRY INGREDIENT PREPARATION……Page 131
SCREW FEEDERS……Page 132
MODIFICATIONS FOR SPECIAL REQUIREMENTS……Page 134
GRAVIMETRIC, OR LOSS IN WEIGHT FEEDING……Page 135
B. HOPPER VOLUME CONSIDERATIONS……Page 137
D. AVOIDING BRIDGING……Page 138
A. GENERAL STATEMENTS……Page 139
C. REFILL ALGORITHM……Page 140
D. AIR DISPLACEMENT……Page 141
E. REFILL DEVICES……Page 142
A. WEIGHT BALANCING……Page 143
B. INFLUENCES OF PRESSURE CHANGES……Page 144
D. RESOLUTION OF THE LOAD CELLS……Page 146
REFERENCES……Page 147
I. INTRODUCTION……Page 148
II. TORQUE RHEOMETER WITH BATCH-MIXING SENSOR……Page 153
A. BATCH DIFFERENTIATION……Page 155
C. SPECIALIZED ADAPTATIONS FOR SPECIFIC TESTING……Page 157
III. TORQUE RHEOMETER WITH TWIN- SCREW EXTRUDER SENSOR……Page 158
B. CLINICAL TRIALS WITHIN A COROTATING, PARALLEL TWIN-SCREW SYSTEM……Page 160
C. MICROCOMPOUNDING……Page 161
IV. TORQUE RHEOMETER WITH SINGLE-SCREW EXTRUDER SENSOR……Page 163
V. SUMMARY……Page 164
I. INTRODUCTION……Page 165
B. TWIN-SCREW EXTRUDERS……Page 166
B. DISSIPATIVE MIX MELTING……Page 169
A. DISPERSIVE MIXING……Page 170
B. DISTRIBUTIVE MIXING……Page 172
VI. DIE PRESSURIZATION……Page 173
VII. PROCESS LENGTH……Page 174
VIII. EXTRUDER CAPACITY……Page 175
IX. PROCESS MODEL……Page 176
A. CONSISTENCY……Page 178
XI. CONCLUSION……Page 179
REFERENCES……Page 180
I. INTRODUCTION……Page 182
II. STRAND PELLETIZERS……Page 183
A. AIR QUENCH DIE FACE PELLETIZERS……Page 185
B. UNDERWATER PELLETIZERS……Page 187
C. WATER RING PELLETIZERS……Page 188
IV. VIBRATING RING DROPPO PELLETIZERS……Page 189
VI. DIE DESIGN ISSUES……Page 190
REFERENCES……Page 192
I. INTRODUCTION……Page 193
II. PROCESS AND EQUIPMENT……Page 195
III. APPLICATIONS TO CONTROLLED- RELEASE ORAL-DOSAGE FORMS……Page 197
IV. SUMMARY……Page 215
REFERENCES……Page 216
I. INTRODUCTION……Page 219
A. FREE EXTRUSION VERSUS VACUUM SIZING……Page 220
B. COOLING/SIZING IN A ‘‘DRY’’ ENVIRONMENT……Page 221
C. COOLING/SIZING IN LIQUID……Page 223
III. TAKEOFF DEVICES TO PULL THE MATERIAL THROUGH THE COOLING MEDIUM……Page 225
A. SHEARS, SAWS, AND CUTTERS……Page 227
B. COIL WINDING FOR PHARMACEUTICAL EXTRUSIONS……Page 232
SUGGESTED READING……Page 234
I. INTRODUCTION……Page 235
II. BASIC CONCEPTS……Page 236
BLOWN FILM……Page 238
CAST FILM……Page 239
ORIENTING……Page 240
ROLL DESIGN……Page 241
LAMINATIONS……Page 242
AIR KNIVES AND EDGE PINNERS……Page 244
SHEET TAKEOFF MACHINES……Page 245
SHEET DIES……Page 247
WEB GUIDING……Page 249
SHEET PROCESSING TIPS……Page 250
REFERENCES……Page 253
I. INTRODUCTION……Page 255
II. SOLID DISPERSIONS……Page 256
A. BACKGROUND……Page 259
B. PROCESS……Page 262
C. MOLECULAR SOLID DISPERSIONS WITH MELT EXTRUSION TECHNOLOGY……Page 263
IN VIVO DATA……Page 265
REFERENCES……Page 266
I. INTRODUCTION……Page 271
B. BALL MILLING……Page 272
E. HOMOGENIZATION……Page 273
G. SURFACTANTS AND WETTING AGENTS……Page 274
IV. PARTICULATE DISPERSIONS……Page 275
A. MELT-EXTRUDED PARTICULATE DISPERSIONS……Page 276
EXAMPLE A……Page 277
EXAMPLE B……Page 280
V. SUMMARY……Page 284
REFERENCES……Page 285
I. INTRODUCTION……Page 287
II. APPLICATIONS……Page 288
III. GENERAL PROCESS DESCRIPTION……Page 290
A. DRY MIXING……Page 291
B. GRANULATION……Page 292
C. EXTRUSION……Page 298
D. SPHERONIZATION……Page 308
V. FORMULATION VARIABLES……Page 313
VI. SCALE AND SCALE-UP……Page 323
REFERENCES……Page 328
I. INTRODUCTION……Page 333
A. WET MASSING……Page 334
III. WET GRANULATION IN BATCH MODE……Page 335
B. WET GRANULATION USING LOW-SHEAR GRANULATORS……Page 336
D. WET GRANULATION USING EXTRUSION SPHERONIZATION……Page 337
IV. WET GRANULATION IN SEMICONTINUOUS MODE……Page 338
V. WET GRANULATION IN CONTINUOUS MODE……Page 339
A. CONTINUOUS FLUIDIZED BED GRANULATORS……Page 340
NIRO AND GLATT CONTINUOUS FLUID BED……Page 341
C. TWIN-SCREW EXTRUDERS……Page 344
GENERAL PROCESS DESCRIPTION AND PROCESS PARAMETERS……Page 347
TSE GRANULATION EXAMPLES……Page 348
VI. CONCLUSIONS……Page 351
REFERENCES……Page 352
I. INTRODUCTION……Page 354
B. CEILING HEIGHT……Page 355
III. COMMISSIONING……Page 356
IV. QUALIFICATION……Page 357
A. INSTALLATION QUALIFICATION……Page 358
PRODUCT CONTACT MATERIALS OF CONSTRUCTION……Page 359
CALIBRATION OF CRITICAL INSTRUMENTS……Page 360
STANDARD OPERATING PROCEDURES……Page 361
SAFETY……Page 362
OPERATING CONTROLS……Page 363
ALARMS/INTERLOCKS……Page 364
C. PERFORMANCE QUALIFICATION……Page 365
D. COMPUTER VALIDATION……Page 366
REFERENCES……Page 367
I. INTRODUCTION……Page 369
II. EXTRUDER TEMPERATURE CONTROL……Page 370
B. LIQUID HEATING……Page 371
D. LIQUID COOLING……Page 373
E. THERMOCOUPLES……Page 374
F. TEMPERATURE CONTROLLERS……Page 376
A. DIRECT CURRENT DRIVES AND MOTORS……Page 377
B. ALTERNATING CURRENT DRIVES AND MOTORS……Page 379
C. DIGITAL DRIVES……Page 382
IV. PROGRAMMABLE LOGIC CONTROLLER AND PERSONAL COMPUTER CONTROL……Page 383
A. PROGRAMMABLE LOGIC CONTROLLER CONTROL……Page 384
V. PROCESS MONITORING……Page 385
C. MELT PRESSURE……Page 386
VI. DATA ACQUISITION AND MONITORING SYSTEMS……Page 388
VII. CONCLUSION……Page 389
REFERENCES……Page 390
I. INTRODUCTION……Page 391
B. SINGLE-SCREW EXTRUDERS……Page 392
E. DOWNSTREAM OPERATIONS……Page 393
F. CONTROLS……Page 395
B. DOSAGE FORM FLEXIBILITY……Page 396
C. EXCIPIENTS……Page 397
E. SCALABILITY……Page 398
IV. CONCLUSION……Page 399
REFERENCES……Page 400