Handbook of Modern Pharmaceutical Analysis (eBook)

Cover 1
CONTENTS 6
CONTRIBUTORS 14
PREFACE 18
Chapter 1. Modern Pharmaceutical Analysis: An Overview 22
I. Identity and Purity Requirements 23
II. Bioavailability/Dissolution Requirements 25
III. Regulatory Considerations 25
IV. Regulatory Compliance 29
V. International Conference on Harmonization 30
VI. Global CMC NDA 30
VII. Highlights of Modern Pharmaceutical Analysis 31
References 43
Chapter 2. Combinatorial Chemistry and High-Throughput Screening in Drug Discovery and Development 44
I. Introduction 45
II. Combinatorial Methods 46
III. Methods for Structural Assignment 47
IV. Diversity 49
V. Druglikeness 49
VI. Designing Combinatorial Libraries with Optimal ADME Properties 49
VII. Existing Computational Methods for ADME Properties 51
VIII. Optimization Philosophy 56
IX. Applying Existing ADME Models to Combinatorial Library Design 58
X. The Future of ADME Modeling 59
XI. High-Throughput Screening and Combinatorial Chemistry 60
XII. Assay Plate Formats: Move to Miniaturization 61
XIII. Nonseparation or Homogeneous Assays 64
XIV. Identification of Receptor Antagonists for Chemokine Receptor and Bradykinin-1 by Screening a 150,000-Member Combinatorial Library 65
XV. Structure-based Design of Somatostatin Agonists 68
XVI. Conclusions 69
References 70
Chapter 3. Solid-State Analysis 78
I. Introduction 78
II. Properties Associated with the Molecular Level 79
III. Properties Associated with the Particulate Level 86
IV. Properties Associated with the Bulk Level 95
V. Summary 102
References 103
Chapter 4. Degradation and Impurity Analysis for Pharmaceutical Drug Candidates 106
I. Residual Solvents and Water 107
II. Purposeful Degradation Studies 116
III. Isolation and Identification of Impurities/Degradants 140
IV. Mass Spectrometry in Identification of Impurities 148
V. Role of NMR 168
VI. Reference Standards 187
VII. Summary 189
References 189
Chapter 5. Preformulation Studies 194
I. Introduction 194
II. Preformulation Studies 201
III. Analytical Techniques and Instruments for Preformulation Studies 235
IV. Regulatory Requirements for Preformulation 245
V. Summary and Conclusions 247
Appendix 1 248
Appendix 2 250
Appendix 3 253
References 253
Chapter 6. Solid Dosage-Form Analysis 256
I. Introduction 256
II. Physicochemical Characterization Techniques 262
III. Near-Infrared Analysis 273
IV. Automation 278
V. Future Directions 283
VI. Summary 284
VII. Acknowledgments 284
References 284
Chapter 7. Parenteral Dosage Forms 290
I. Characteristics of Parenteral Dosage Forms 291
II. Pharmaceutical Analysis During Formulation and Process Development 292
III. Analytical Testing for Finished Parenteral Products 293
IV. Packaging Components Testing 294
V. Process Development Support 295
VI. In-Process Testing 296
VII. Release Testing 296
VIII. Raw Material Testing 299
IX. Validation of Analytical Procedure 300
X. Stability-Indicating Methods 302
XI. Method Transfer 302
XII. Cleaning Method Validation 303
XIII. Admixture Studies 303
XIV. Microbiological Testing of Parenteral Formulations 304
XV. Sterility Testing 305
XVI. Bacterial Endotoxin Testing 311
XVII. Particulate Matter Testing 313
XVIII. Bioburden Testing of Parenteral Product Solution 315
XIX. Introduction to Cleaning Validation 319
XX. Swab Selection (Recovery and Compatability Studies) 319
XXI. Technician Qualification 319
XXII. Sampling 320
XXIII. Acceptance Criteria 321
XXIV. Methods of Analysis 322
XXV. Grouping/Matrix Approach 322
XXVI. Validation Protocol 323
XXVII. Validation Report 323
XXVIII. Summary 323
References 324
Chapter 8. New Drug Delivery Systems 328
I. Introduction 328
II. Oral Drug Delivery 329
III. Direct Drug Delivery 331
IV. Dermatological Delivery System 332
V. Tumor-Targeted Drug Delivery Systems 332
VI. Biodegradable Drug Delivery System 334
VII. Protein Drug Delivery System 336
VIII. Devices 340
IX. Summary 344
References 344
Chapter 9. Compendial Testing 346
I. Introduction 346
II. A Brief History of the United States Pharmacopeia 347
III. Compendial Testing for Formulated Products and Active Ingredients 348
IV. Which Compendium to Use and When to Use It 361
V. Validation 361
VI. Harmonization of Testing Methods for Multicountry Submission 363
VII. Conclusions 364
VIII. Acknowledgments 365
References 365
Chapter 10. Method Development 366
I. Introduction 366
II. Overview of Separation Methods 367
III. High-Performance Liquid Chromatography 370
IV. Thin-Layer Chromatography 395
V. Gas Chromatography 396
VI. Supercritical-Fluid Chromatography 397
VII. Capillary Electrophoresis 400
VIII. Conclusions 404
IX. Summary 404
References 405
Chapter 11. Setting Up Specifications 408
I. Introduction 408
II. Setting Specifications at Different Stages of Drug Development 410
III. International Conference on Harmonization Guidelines 414
IV. Pharmacopeias and Specifications 431
V. Statistical Considerations in Setting Specifications 432
VI. Summary 433
References 433
Chapter 12. Validation of Pharmaceutical Test Methods 436
I. Background and Chapter Overview 436
II. Validation Terminology and Definitions 439
III. Method Development and Its Influence on Method Validation 440
IV. Validation Requirements of The Method 449
V. Validation Documentation 449
VI. Validation Experimentation 450
VII. Method Transfer 457
VIII. Revalidation 459
IX. Reference Standards 459
X. Summary 462
Acknowledgments 462
References 10
Chapter 13. Stability Studies 466
I. Introduction 466
II. Operational Issues 467
III. Excipients 482
IV. Drug Substance 484
V. Drug Product 492
VI. Summary 501
Glossary 501
Appendix 503
References 504
Chapter 14. Analytical Methodology Transfer 506
I. Introduction 506
II. The Drug Development Process 507
III. Types of Method Transfer 508
IV. Requirements and Elements of Analytical Technology Transfer 510
V. Technical Transfer Time Line/Project Plan 513
VI. Analysis of Results/Statistical Packages 514
VII. Analyst Certification and Training 515
VIII. Transfer of Technical Ownership 515
IX. Chapter Summary 518
References 518
Chapter 15. Pharmaceutical Analysis Documentation 520
I. Scope 520
II. Introduction 521
III. Pharmaceutical Analysis During Product Life Cycle 521
IV. Regulatory Documents 531
V. Compliance Documents 537
VI. Research Documents 541
VII. Summary 542
VIII. Conclusions 543
Appendix I: References for CMC Guidances 543
Appendix II: U.S. NDA Table of Contents„Analytical Documentation 546
Chapter 16. An Innovative Separation Platform: Electrophoretic Microchip Technology 550
I. Introduction 550
II. Microchip Fabrication 552
III. Detection Techniques 556
IV. Pharmaceutical Potential 566
V. Concluding Remarks 570
VI. Summary 570
References 570
INDEX 576