Parenteral Products (eBook)

Front Cover 1
Parenteral Products 2
Copyright Page 3
Dedication 4
Preface 6
Table of Contents 8
Chapter 1. Perspective on the Use of Parenteral Solutions 10
INTRODUCTION 10
ROUTES OF ADMINISTRATION 11
THE EFFECT OF ROUTE ON THE DURATION OF DRUG ACTIVITY 12
THE 'HYDROSPRAY' INJECTOR 12
THE ORIGINS OF THE INTRAVENOUS THERAPY 13
THE DEVELOPMENT OF HYPODERMIC MEDICATION 16
THE STERILIZATION OF INJECTION SOLUTIONS 18
THE UNITED STATES PHARMACOPOEIAL CLARITY TEST 20
REFERENCES 22
Chapter 2. The Formulation of Parenteral Products 24
UNITS 24
THE TONICITY OF INJECTION SOLUTIONS 25
THE ELECTROLYTE COMPOSITION OF BODY FLUIDS 27
THE CHOICE OF SOLVENT 28
OILY SOLVENTS 31
COLLOIDAL DISPERSIONS 33
SOLUBILIZED PRODUCTS 33
STABILIZERS 34
PARENTERAL SUSPENSIONS 35
THE FORMULATION OF PARENTERAL EMULSIONS 39
THE PHYSICAL PROPERTIES OF EMULSIONS 39
FORMULATION CONSIDERATIONS 40
WATER-IN-OIL-EMULSIONS 44
PREPARATION 44
TOXICITY 45
STABILITY 46
PACKING 46
METHOD OF .D...ISTRATION 47
THE APPLICATION OF INTRAVENOUS EMULSIONS 47
AMINO ACIDS AND OTHER PARENTERAL NUTRIENTS 49
THE 'BROWNING' REACTION OF D-GLUCOSE ON AUTOCLAVING 52
REFERENCES 54
Chapter 3. Filtration 57
INTRODUCTION 57
CLASSIFICATION OF FILTRATION OPERATIONS 59
SCREEN FILTERS 59
DEPTH FILTERS 59
CAKE FILTERS 60
THEORIES OF FILTRATION 60
MECHANISM OF PARTICLE CAPTURE 62
THE RELATIVE ADVANTAGES AND DISADVANTAGES OF SCREEN AND DEPTH FILTERS 63
PRETREATMENT 64
THE CRITERIA OF AN IDEAL FILTER 65
THE CHOICE OF FILTRATION MEDIA 65
CELLULOSE PAPERS 66
ASBESTOS PADS AND PAPERS 66
SINTERED GLASS FILTERS 68
SINTERED METAL FILTERS 68
GLASS PAPERS 69
MEMBRANE FILTERS 70
PREPARATION OF A MEMBRANE FILTER 70
THE STRUCTURE OF CELLULOSE MEMBRANE FILTERS 71
THE MECHANISMS OF MEMBRANE FILTRATION 74
THE TESTING OF MEMBRANE FILTERS 75
THE ADVANTAGES OF MEMBRANE FILTERS 77
THE TYPES AND SHAPES OF MEMBRANE FILTERS AT PRESENT AVAILABLE 78
DISCUSSION: THE CHOICE OF A FILTRATION SYSTEM FOR PARENTERAL PRODUCTS 84
REFERENCES 92
Chapter 4. Sterilization 94
INTRODUCTION 94
THE MEANING OF STERILIZATION 94
METHODS OF STERILIZATION DESTRUCTION 95
'KILLING' OR INACTIVATION 96
PHYSICAL REMOVAL 97
THE KINETICS OF MICROBIAL DEATH INTRODUCTION 98
FIRST ORDER OF REACTION 99
THERMAL DEATH TIME 101
DECIMAL REDUCTION TIME (D VALUE) 102
THERMAL DESTRUCTION VALUE (Z VALUE) 102
THE Q-10 VALUE 103
INACTIVATION FACTORS 103
THE NON-KINETIC F VALUE 104
FACTORS AFFECTING THE SURVIVAL OF MICRO-ORGANISMS 105
THE CONTROL OF STERILIZATION PROCESSES 106
THE STEAM AUTOCLAVE INTRODUCTION 108
VACUUM-PURGED AUTOCLAVES AND BALLASTED AUTOCLAVES 109
SPRAY COOLED AUTOCLAVES 110
DISADVANTAGES OF DISCONTINUOUS AUTOCLAVES 111
CONTINUOUS AUTOCLAVES INTRODUCTION 112
THE 'HYDROMATIC' STERILIZER 115
THE ECONOMICS OF CONTINUOUS AUTOCLAVING 118
OVERPRESSURE STERILIZERS 119
REFERENCES 120
Chapter 5. The Working Environment 121
INTRODUCTION 121
THE MANUFACTURING PROCESS STRUCTURE OF A PHARMACEUTICAL MANUFACTURER 122
THE ECONOMICS OF PRODUCTION 123
THE ASSEMBLY OF CONSTITUENTS AND COMPONENTS 126
MANUFACTURING 128
THE IMPORTANCE OF QUALITY CONTROL 131
CODES OF GOOD MANUFACTURING PRACTICE 134
CLEAN WATER INTRODUCTION 137
'WATER FOR INJECTIONS' 138
DISTILLED WATER 139
ION EXCHANGE COLUMNS 139
FILTRATION METHODS 140
MODERN METHODS OF PRODUCING LARGE QUANTITIES OF STERILE, ULTRA-PURE WATER 142
CLEAN CONTAINERS GLASS 144
CHEMICAL PROPERTIES OF GLASS 144
THE CLEANING OF GLASS 145
SEALANTS THE CHEMICAL CONSTITUENTS OF RUBBER 147
THE CLEANING OF RUBBER SEALANTS 149
THE POST-WASHING TREATMENT OF RUBBER 150
PLASTICS 150
TYPES OF PLASTIC SUITABLE FOR IV SOLUTIONS 151
THE ADVANTAGES OF PLASTIC CONTAINERS FOR INTRAVENOUS FLUIDS 153
DISADVANTAGES OF PLASTIC CONTAINERS 153
THE COMBINED BLOWING AND FILLING OF PLASTIC CONTAINERS 155
CLEAN AIR INTRODUCTION 155
THE MECHANISM OF GASEOUS FILTRATION 158
GASEOUS FILTRATION MEDIA 159
THE 'HIGH-EFFICIENCY PARTICULATE AIR' (HEPA) FILTERS 160
THE TESTING OF AIR FILTERS 161
CHEMICAL METHODS OF STERILIZING AIR 162
LAMINAR FLOW CABINETS INTRODUCTION 162
THEORY 163
STANDARDS FOR LAMINAR FLOW UNITS 165
CONSTRUCTION OF LAMINAR FLOW CABINETS 165
THE APPLICATION OF LAMINAR FLOW UNITS 168
CLEAN ROOMS CONVENTIONAL CLEAN ROOMS 169
THE DESIGN AND CONSTRUCTION OF CLEAN ROOMS 170
THE HUMAN FACTOR 171
LAMINAR FLOW CLEAN ROOMS 174
REFERENCES 175
Chapter 6. The Monitoring and Control of Particulate Contamination 177
INTRODUCTION 177
SAMPLING 178
THE PARTICLE SIZE OF PARTICULATE CONTAMINATION 180
VISUAL METHODS OF INSPECTION 181
THE SIZE OF PARTICLES VISIBLE TO THE UNAIDED EYE 185
THE RELIABILITY OF VISUAL INSPECTION METHODS 186
PROJECTION METHODS FOR THE INSPECTION OF AMPOULES 187
THE INSPECTION OF PLASTIC CONTAINERS 188
MACHINE METHODS USED FOR THE INSPECTION OF AMPOULES MADE ON THE LARGE SCALE 188
AUTOMATIC OR SEMI-AUTOMATIC INSPECTION METHODS FOR THE INSPECTION OF AMPOULES MADE ON A LARGE SCALE 190
FILTRATION METHODS AND THE IDENTIFICATION OF CONTAMINATION 193
THE MILLIPORE SAMPLING METHODS 194
AN ALTERNATIVE PROCEDURE USING TRANSMITTED LIGHT 195
THE ADVANTAGES OF FILTRATION PROCEDURES 196
THE IDENTIFICATION OF PARTICULATE CONTAMINATION 197
SOME APPLICATIONS OF FILTRATION ANALYSIS 197
OTHER METHODS OF MEASURING THE RESIDUE COLLECTED ON A FILTER 198
ELECTRICAL SENSING ZONE METHODS OF ANALYSIS INTRODUCTION 201
THE COULTER PRINCIPLE 201
THE RANGE OF SIZE MEASURED BY THE COULTER COUNTER 203
THE RANGE OF APPLICATION TO PARENTERAL PRODUCTS 203
INSTRUMENT CALIBRATION 204
PROBLEMS OF USING A COULTER COUNTER PROCEDURE FOR CARRYING OUT A STANDARD TEST 205
THE RESPONSE OF DIFFERENT COULTER COUNTERS TO SINGLE STIMULI 206
METHODS OF USING THE COULTER COUNTER FOR THE MEASUREMENT OF CONTAMINATION 208
THE APPLICATION OF THE COULTER PRINCIPLE TO MEASUREMENT OF CONTAMINATION 213
TURBIDIMETERS AND NEPHELOMETERS 214
OTHER INSTRUMENTS USING LIGHT SCATTERING PRINCIPLES OF DETECTION 218
DETECTION OF PARTICLES BY THE LIGHT-BLOCKAGE PRINCIPLE 222
CALIBRATION AND THEORY OF THE LIGHT BLOCKAGE METHOD 224
THE PRACTICAL APPLICATION OF LIGHT-BLOCKAGE METHODS TO ASSESSMENT OF PARTICULATE CONTAMINATION 225
DETECTION OF PARTICULATE CONTAMINATION BY MEANS OF A SCREEN FILTRATION PRESSURE METHOD 226
CONCLUSIONS 228
REFERENCES 229
Appendix One 233
Chapter 7. The Size Distribution of Particulate Contamination and Standards of Cleanliness 236
INTRODUCTION 236
THE SIZE DISTRIBUTION OF POWDERS AND POWDERED MATERIALS 237
THE SIZE DISTRIBUTION OF AIR-BORNE DUSTS 239
THE SIZE AND DISTRIBUTION OF FRACTURED MATERIALS 241
SIZE DISTRIBUTION IN HYDRAULIC SYSTEMS 241
THE EXPERIMENTAL EVIDENCE FOR THE SIZE DISTRIBUTION OF CONTAMINATION IN PARENTERAL SOLUTIONS 242
THE EPHEMERAL NATURE OF PARTICULATE CONTAMINATION 248
SUGGESTED STANDARDS OF CLEANLINESS SINGLE-POINT STANDARDS 252
MULTI-POINT STANDARDS 254
COMPLEX STANDARDS 254
APPLICATIONS OF STANDARDS AND THE LOG-LOG SIZE DISTRIBUTION 256
PROGRESS TOWARDS AN OBJECTIVE STANDARD OF CLEANLINESS 257
DISCUSSION: THE PROBLEMS OF APPLYING STANDARDS FOR CLEANLINESS 259
REFERENCES 262
Chapter 8. The Nature, Origin and Hazards of Particulate Contamination 265
...RODUCTION 265
NATURE AND ORIGIN OF PARTICULATE CONTAMINATION 265
THE SIZE AND NUMBER OF CONTAMINATING PARTICLES 268
THE HAZARD DUE TO INJECTED PARTICULATE CONTAMINATION 269
EXPERIMENTAL EVIDENCE 272
CONCLUSION 275
REFERENCES 275
Chapter 9. Pharmaceutical Problems associated with the Administration of Large Volume Parenteral Fluids 278
INTRODUCTION THE SETTING UP OF A LARGE VOLUME DRIP SOLUTION 278
THE CLEANLINESS OF INTRAVENOUS SOLUTOIN GIVING SETS 283
STERILE AIR FILTERS 285
PHARMACEUTICAL INCOMPATIBILITIES OF DRUGS ADDED TO INTRAVENOUS SOLUTIONS 286
TYPES OF INCOMPATIBILITY ENCOUNTERED IN INTRAVENOUS SOLUTIONS 287
PHYSICAL INCOMPATIBILITY 288
CHEMICAL INCOMPATIBILITY 289
FACTORS AFFECTING CHEMICAL REACTIONS IN INTRAVENOUS FLUIDS 290
THE INFLUENCE OF pH ON THE SOLUBILITY OF ADDITIVES 291
THE INFLUENCE OF pH ON THE STABILITY OF ADDITIVES 293
OTHER FACTORS TO BE CONSIDERED WHEN MAKING ADDITIONS TO INTRAVENOUS FLUIDS 295
MINIMIZATION OF INCOMPATIBILITY REACTIONS 297
THE LOSS OF THERAPEUTIC EFFECTIVENESS OF DRUGS DURING ADMINISTRATON 299
MICROBIOLOGICAL HAZARDS ASSOCIATED WITH INTRAVENOUS FLUID THERAPY 302
INADEQUATE STERILIZABON PROCEDURES 303
INADEQUATE PACKS 304
FAULTY PACKS 304
FAULTY TECHNIQUE 305
THE INSPECTION OF CONTAINERS AND GIVING SETS PRIOR TO ADMINISTRABON 305
THE USE OF TERMINAL FILTERS INTRODUCTION 307
REUSABLE FILTER UNITS, INCLUDING THOSE DESIGNED TO BE ATTACHED TO SYRINGES 309
DISPOSABLE TERMINAL FILTER UNITS FOR INTRAVENOUS SOLUTONS 311
THE EFFEOTVENESS OF TERMINAL FILTERS MICROBIAL 313
PARTICULATE 313
THE IMPLICATIONS OF PHARMACEUTICAL INCOMPA.BILITIES FOR THE HOSPITAL PHARMACEUTICAL SERVICE 315
REFERENCES 317
Index 320