Quality Control of Medicines (eBook)

Front Cover 1
The Quality Control of Medicines 4
Copyright Page 5
Table of Contents 12
Introduction 6
List of contributors 8
Inaugural address 16
The quality control of medicines: A national and international responsibility 16
Part I: Main symposium. The basis for the quality control of medicines 24
Chapter 1. Chemical And Physical Aspects Of The Control Of Medicines 24
RESEARCH AND DEVELOPMENT 25
PHARMACEUTICAL PREPARATIONS 34
AUTOMATION 36
CONCLUSION 37
SUMMARY 38
Chapter 2. Biological Aspects Of The Control Of Medicines 40
ANTIGEN ANTIBODY REACTION 46
REFERENCES 57
Chapter 3. New concepts and standards of quality control as applied to controlled drug delivery systems 60
INTRODUCTION 60
QUALITY STANDARDS AND CONTROL METHODS FOR POLYMERIC MATERIALS 65
STANDARDS AND CONTROL METHODS IN DELIVERY SYSTEM MANUFACTURING OPERATIONS 67
STERILIZATION METHODS AND STERILITY STANDARDS 70
"FUNCTIONALITY": CONTROL METHODS AND STANDARDS 71
CONCLUSIONS 77
SUMMARY 78
Chapter 4. Storage problems associated with the control of medicines 80
SUPERVISION AND PROLONGATION OF STORABILITY 91
REFERENCES 96
Chapter 5. International problems in the control of medicines 98
Part II: Parallel symposia 112
Section 1: Physicochemical analysis 112
Chapter 
112 
RECALL OF THE FUNDAMENTAL PRINCIPLES 112
INTRODUCTION TO THE EXPERIMENTAL METHOD 116
CHARACTERISTICS OF FLUORESCENT MOLECULES 117
ANALYTICAL APPLICATIONS 119
COMPARISON OF FLUORESCENCE WITH OTHER SPECTRAL METHODS 123
ENVIRONMENTAL EFFECTS AND LIMITATIONS 124
CONCLUSIONS 128
ACKNOWLEDGEMENTS 129
REFERENCES 130
Chapter 
132 
INTRODUCTION 132
DETECTION LIMIT, IDENTIFICATION LIMIT AND SAMPLE AMOUNTS. DERIVATISATION-REACTIONS 134
USES IN THE QUALITY CONTROL OF DRUGS 137
PROCEDURE FOR MASS SPECTROMETRIC IONISATION 141
COMBINATIONS OF MASS SPECTROMETRY WITH CHROMATOGRAPHIC SEPARATION PROCEDURES 146
REFERENCES 152
Chapter 
156 
THE MICROWAVE GAS DISCHARGE 157
AFTERGLOW EXCITED MOLECULAR EMISSION SPECTRA 163
REFERENCES 166
Chapter 
168 
DATA PROCESSING IN THE ADMINISTRATIVE ASPECT OF PHARMACEUTICAL QUALITY CONTROL 168
DATA PROCESSING IN THE LABORATORY 171
AUTOMATIC ANALYSERS 173
PREFERRED RANGES FOR THE USE OF AUTOMATIC ANALYSERS 180
CONCLUDING REMARKS 185
REFERENCES 185
Section 2: Microbiological aspects 188
Chapter 
188 
INTRODUCTION 188
CONCLUSIONS 202
REFERENCES 202
Chapter 
204 
INTRODUCTION 204
MICROBIOLOGICAL PURITY-STANDARDS OF NON-STERILE PRODUCT 204
PRODUCT 205
MICROBIOLOGICAL ASPECTS IN THE DEVELOPMENT OF A PRODUCT 208
QUALITY ASSURANCE SYSTEM 211
REFERENCES 212
Chapter 
214 
STERILITY REQUIREMENTS FOR OPHTHALMIC PREPARATIONS 214
WHEN AND WHY IS PRESERVATION REQUIRED? 216
THE FINAL CONTAINER 227
REFERENCES 227
Section 3: Bioavailability testing 230
Chapter 
pharmacokinetic considerations 230
INTRODUCTION 230
CHOICE OF PARAMETERS TO BE MEASURED 231
CHOICE OF THE GALENICAL FORM FOR THE INITIAL CLINICAL STUDIES 233
CRITERIA GOVERNING THE SELECTION OF VOLUNTEERS FOR BIOAVAILABILITY TESTING 234
CONSIDERATIONS FOR INTRAVENOUS INJECTIONS 237
METHODOLOGY OF THE MEASUREMENT OF BIOAVAILABILITY LEVELS 238
BIOAVAILABILITY SPEED MEASUREMENT METHODOLOGY 243
CONCLUSIONS 245
REFERENCES 247
Chapter 
pharmacological and clinical measurements 250
USE OF CLINICAL RESPONSE TO OBJECTIVELY ASSESS CLINICAL SIGNIFICANCE OF BIOINEQUIVALENCIES 250
USE OF CLINICAL AND PHARMACOLOGICAL RESPONSE TO DETECT AND QUANTITATE BIOAVAILABILITY 254
USE OF CLINICAL DATA TO DETERMINE OPTIMUM DOSAGE FORM AND BLOOD LEVEL MEASUREMENTS RELATIVE TO PARENT DRUG AND METABOLITE ACTIVITY 255
CLINICAL USE VARIABLES 257
REFERENCES 258
Chapter 
260 
INTRODUCTION 260
CHROMATOGRAPHIC TECHNIQUES 261
RADIOACTIVE TECHNIQUES 265
CONCLUSION 266
Chapter 16. In vitro studies on the dissolution and absorption behaviour of orally administered drugs and the connection to their bioavailability 268
INTRODUCTION 268
GASTROINTESTINAL DISSOLUTION FACTORS 269
PHYSICAL IN VITRO MODELS OF THE GASTROINTESTINAL TRACT FOR THESTUDY OF DRUG DISSOLUTION 271
INTERACTION OF PHYSIOLOGICAL FACTORS OR CHARACTERISTICS OF THE APPARATUS ON DRUG DISSOLUTION 274
INTERPRETATION OF DISSOLUTION CURVES 276
COMPARATIVE IN VIVO - IN VITRO STUDIES ON THE EFFECT OF THE DISSOLUTION FACTOR AGITATION 279
ABSORPTION CHARACTERISTICS SIMULATED IN VITRO 282
IN VITRO MODEL STUDIES OF THE FUTURE 285
SUMMARY 285
REFERENCES 286
Chapter 17. Bioavailability: a challenge to the standard concept of regulating the quality of drug products by published monographs 288
INTRODUCTION 288
BIOAVAILABILITY CHALLENGE 289
WAYS TO ASSESS BIOAVAILABILITY 290
COMPENDIAL ACTIVITY 291
FDA PROPOSED BIOAVAILABILITY REGULATIONS 292
MANY DRUGS COVERED 292
DETERMINANT FACTORS 293
SCOPE OF PROPOSED CONTROLS 293
LIMITATIONS OF IN VITRO TESTING 294
PROLONGED IMPLEMENTATION PERIOD 296
THE DIGOXIN INCIDENT 297
CONCLUSION 298
Section 4: Separation techniques 302
Chapter 18. Ion-pair and complex extraction of organic compounds 302
CONTROL OF THE EXTRACTION DEGREE 302
ORGANIC SOLVENT EFFECTS 307
ION-PAIR STRUCTURE AND EXTRACTION CONSTANT 309
EXTRACTION OF HYDROPHILIC IONS 311
OPTICAL DETERMINATION TECHNIQUE 312
ION-PAIR PARTITION LIQUID CHROMATOGRAPHY 313
CHROMATOGRAPHIC APPLICATIONS 313
AMPLIFICATION OF THE DETECTOR RESPONSE 316
BIOLOGICAL SAMPLES 317
REVERSED PHASE SYSTEMS 317
REFERENCES 320
Chapter 
322 
INTRODUCTION 322
LITERATURE REVIEW 322
GENERAL ASPECTS PERTAINING TO ANALYTICAL THIN-LAYER CHROMATOGRAPHY 326
OBJECT OF THIN-LAYER CHROMATOGRAPHIC PURITY TESTS 328
PHARMACOPOEIAL METHODS 328
METHODS FOR NON-COMPENDIAL USE 332
CONCLUDING REMARKS 332
REFERENCES 333
Chapter 20. Problems relating to the interpretation of spectroscopic data in the presence of degradation products 336
SUFFICIENT QUALITY OF THE ADJUSTMENT 340
Chapter 
352 
INTRODUCTION 352
SEPARATION MECHANISMS 355
MOLECULAR SIZING 357
ADSORPTION ON SURFACE 357
ADSORPTION ON MOLECULES STRONGLY ADSORBED TO THE SURFACE 358
CHEMICALLY BONDED THIN LAYER 358
ADSORPTION ON THICK LAYERS OF STATIONARY PHASE 359
POROUS MATRIX PACKINGS 359
CHROMATOGRAPHIC PACKING CHARACTERISTICS 359
ROLE OF THE ELUENT 360
PREPARATIVE LIQUID CHROMATOGRAPHY 362
REFERENCES 363
Section 5: Submissions to regulatory bodies and international aspects of drugcontrol 366
Chapter 
366 
Chapter 
376 
THE ASSESSMENT OF DRUGS FOR SAFETY AND EFFICACY PRIOR TOMARKETING 377
THE MONITORING OF THE EFFECTS OF DRUGS ON THE MARKET 379
Chapter 
390 
Chapter 
398 
Subject index 408