Overview

There are unique challenges in the formulation, manufacture, analytical chemistry, and regulatory requirements of low-dose drugs. This book provides an overview of this specialized field and combines formulation, analytical, and regulatory aspects of low-dose development into a single reference book. It describes analytical methodologies like dissolution testing, solid state NMR, Raman microscopy, and LC-MS and presents manufacturing techniques such as granulation, compaction, and compression. Complete with case studies and a discussion of regulatory requirements, this is a core reference for pharmaceutical scientists, regulators, and graduate students.

Full Product Details

Author:   Jack Zheng
Publisher:   John Wiley & Sons Inc
Imprint:   John Wiley & Sons Inc
Dimensions:   Width: 16.30cm , Height: 2.80cm , Length: 24.30cm
Weight:   0.798kg
ISBN:  

9780470056097

ISBN 10:   0470056096
Pages:   500
Publication Date:   10 March 2009
Audience:   Professional and scholarly ,  Professional & Vocational
Format:   Hardback
Publisher's Status:   Active
Availability:   Out of stock  
The supplier is temporarily out of stock of this item. It will be ordered for you on backorder and shipped when it becomes available.

Table of Contents

Preface xv Foreword xix Contributors xxi 1 An Overview 1 Jack Y. Zheng 1.1 The Drug Discovery and Development Process 2 1.2 Challenges and Strategies in Development of Low-Dose Drug Products 10 1.3 Summary 20 Acknowledgments 20 References 20 I Challenges and Strategies In Formulation Development of Oral Low-Dose Drug Products 23 2 Challenges and Strategies In Formulation Development of Oral Solid Low-Dose Drug Products 25 Jack Y. Zheng 2.1 Introduction 25 2.2 Current Regulatory Environment and its Impact on New Drug Product Development 28 2.3 Challenges in Developing Low-Dose Formulations 31 2.4 Manufacturing Platforms for Low-Dose Drug Products 38 2.5 Use of Experimental Design in Formulation and Process Development 42 2.6 Containments 44 2.7 Summary 45 Acknowledgments 46 References 46 3 Particle Size of Drug Substance and Product Content Uniformity—Theoretical Considerations 49 Kevin C. Johnson 3.1 Introduction 49 3.2 Concept of Ideal Mixing 50 3.3 Ideal Mixing Model Comparison with the Yalkowsky and Bolton Approach 56 3.4 Experimental Support of Model Assumptions 59 3.5 Analytical and Practical Considerations 61 References 62 4 Development of Low-Dose Formulations Using Fluidized Bed Granulation 63 J. Joe Zhou and Ralph Lipp 4.1 Introduction 63 4.2 Granulation Fundamentals 66 4.3 Theory of Fluidization 68 4.4 Formulation Development 72 4.5 Process Development 77 4.6 Summary 86 References 86 5 Development of Low-Dose Solid Oral Formulations Using Wet Granulation 89 Ahmad Almaya 5.1 Introduction 89 5.2 Granulation Mechanisms 91 5.3 General Considerations on Wet Granulation 93 5.4 Advantages and Disadvantages of Wet Granulation 100 5.5 Use of Wet Granulation for Low-Dose Formulations 101 5.6 Process-Induced Form Changes in Wet Granulation 109 5.7 Concluding Remarks 111 References 112 6 Challenges In Development and Scale-Up of Low-Dose Drug Products By Dry Granulation: A Case Study 117 Mary T. Am Ende, Daniel O. Blackwood, Daniel S. Gierer, and Christopher P. Neu 6.1 Introduction 117 6.2 Dry Granulation Process—Pros and Cons 118 6.3 Overview of Dry Granulation Processes and Equipment Design 119 6.4 Challenges for Low-Dose Product Development and their Assessment Methods 125 6.5 Case Study: Formulation Challenges for Low-Dose Products 128 6.6 Process Challenges During Dry Granulation Optimization for Low-Dose Products 140 6.7 Conclusions 154 Acknowledgments 155 References 155 7 Development of Low-Dose Solid Oral Tablets Using Direct Compression 159 Jack Y. Zheng and Robert L. Ternik 7.1 Introduction 159 7.2 Advantages of Direct Compression 160 7.3 Challenges in Low-Dose Tablet Development Using Direct Compression 162 7.4 Formulation Development for Low-Dose Drug Products Using Direct Compression 169 7.5 Manufacturing Process Development for Low-Dose Drug Products 187 7.6 Scale-Up for Blending Operation 196 7.7 Formulation Examples for Direct Compression 197 7.8 Conclusions 199 Acknowledgments 199 References 200 8 Reduction of Particle Size of Drug Substance For Low-Dose Drug Products 205 Christopher L. Burcham, Paul C. Collins, Daniel J. Jarmer, and Kevin D. Seibert 8.1 Introduction 205 8.2 Reduction of Particle Size of Drug Substance by Milling Technologies 207 8.3 Reduction of Particle Size of Drug Substance Using Crystallization Technologies 216 8.4 Scale-Up Considerations 218 8.5 Emerging Technologies and Future Directions 219 Acknowledgments 219 References 219 9 Function, Quality, and Regulations of Pharmaceutical Excipients For Oral Solid Dosage Forms 223 Jack Y. Zheng 9.1 Introduction 223 9.2 Classification of Pharmaceutical Excipients in Solid Dosage Forms 224 9.3 Physicochemical Attributes of Pharmaceutical Excipients 225 9.4 Regulatory Status and Excipient Quality 228 9.5 Summary 235 Acknowledgments 235 References 236 II Challenges In Analytical Method Development For Oral Low-Dose Drug Products 239 10 Analytical Method Development: Challenges and Solutions For Low-Dose Oral Dosage Forms 241 Beverly Nickerson, Reena M. Joseph, Charles Palmer, Alex M. Opio, and George H. Beresford 10.1 Introduction 241 10.2 Case Study 1: Drug Adsorption to Surfaces 242 10.3 Case Study 2: Challenges Due to Nondrug-Related Impurities 245 10.4 Case Study 3: HPLC Purity Method Development Challenges for a Fixed Combination Product Containing a Low-Dose Active Ingredient and a High-Dose Active Ingredient 250 10.5 Case Study 4: Small Volume Dissolution Testing 255 10.6 Summary 261 Acknowledgments 261 References 261 11 In Vitro Dissolution Testing and Method Development 265 Vivian A. Gray, Jack Y. Zheng, and Norman N. Sesi 11.1 Introduction 265 11.2 Overview of Dissolution Testing 265 11.3 Dissolution Method Development 271 11.4 Dissolution Method Development for Low-Dose Oral Drug Products 275 11.5 Summary 279 References 280 12 Analysis of Physical Transformation of Api During Manufacture and Storage 283 Gregory A. Stephenson 12.1 Introduction 283 12.2 Discussion of Solid-State Forms 284 12.3 Monitoring Processing Steps 285 12.4 Measuring Transitions and Solid-Form Transformations in the Low-Dose Tablet 287 12.5 Common Methods Used for Examination of Solid Forms 289 12.6 Conclusions 305 References 306 13 Physical Characterization Tests For Drug Substances Used In Low-Dose Formulations 309 Ronald G. Iacocca 13.1 General Issues in the Physical Characterization of Micronized Powders Used in Low-Dose Formulations 309 13.2 Particle Size Analysis 309 13.3 Specific Surface Area Analysis 320 13.4 Summary 323 References 323 14 An Excipient Library Approach To Analytical Development For Low-Dose, Solid Oral Dosage Form Drug Products 327 Qing Chang, Lisheng Kang, Keri Varner, Joyce Bridges, Norman Sesi, and Margo Palmieri 14.1 Introduction 327 14.2 Importance of Excipient Absorbance Background to Low-Dose Impurity Analysis 328 14.3 Factors Affecting Excipient Absorbance Background 332 14.4 Use of Excipient Library 339 14.5 Conclusions 341 Acknowledgments 341 References 342 15 Cleaning Verification For Highly Potent Compounds 345 Brian W. Pack 15.1 Introduction 345 15.2 Cleaning Validation vs Cleaning Verification 346 15.3 Acceptance Limit Calculations 347 15.4 Analytical Method Validation 352 15.5 General Analytical Techniques 361 15.6 Analytical Techniques for Low-Dose Compounds 364 15.7 Conclusions 376 Acknowledgments 377 References 377 III Containment Techniques For Highly Potent Pharmaceutical Compounds 381 16 Containment Challenges and Strategies For Potent Compounds In The Pharmaceutical Industry 383 Victoria Cathcart, Sarah Jones, and Beverly Nickerson 16.1 Introduction 383 16.2 Safe Exposure Control Levels—Bands, Limits, and Handling Guidance 384 16.3 The Hierarchy of Workplace Controls 389 16.4 Case Studies 397 16.5 Summary 403 Acknowledgments 403 References 403 17 Sample Handling and Containment In Analytical Testing Laboratories 405 David S. Pattavina, Nancy Sage, and Beverly Nickerson 17.1 Introduction 405 17.2 Sample Handling Considerations 406 17.3 Handling Potent Compounds in Standard Analytical Laboratories 407 17.4 Handling Potent Compounds in a Containment Laboratory 411 17.5 Additional Considerations for Handling Potent Materials 426 17.6 Summary 427                                                                                                                                                Acknowledgments 428 References 428 IV Regulatory Considerations In The Development of Low-Dose Drug Products 429 18 Regulatory Considerations In The Development of Low-Dose Solid Oral Drug Products 431 Ravi S. Harapanhalli 18.1 Introduction and Overview 431 18.2 Three-Pronged Approach to Low-Dose Formulations 433 18.3 Pharmaceutical Development Report 434 18.4 Facility Controls for Highly Potent Drugs 451 18.5 Conclusion 452 References 453 Index 455

Reviews

Author Information

Jack Zheng, PhD, is Research Advisor and Team Leader in the Pharmaceutical Sciences R&D Division of Eli Lilly and Company and Adjunct Professor at Beijing University. Dr. Zheng is the author of more than thirty articles and several book chapters. He has been invited to present his work at numerous national and international scientific meetings. He was involved in more than ten new drug product development and regulatory filing with the Food and Drug Administration.

Tab Content 6

Author Website:  

Countries Available

All regions