{"product_id":"formulation-and-analytical-development-for-low-dose-oral-drug-products-isbn-9780470056097","title":"Formulation and Analytical Development for Low-Dose Oral Drug Products","description":"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. \u003cp\u003ePreface xv\u003c\/p\u003e \u003cp\u003eForeword xix\u003c\/p\u003e \u003cp\u003eContributors xxi\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 An Overview 1\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eJack Y. Zheng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 The Drug Discovery and Development Process 2\u003c\/p\u003e \u003cp\u003e1.2 Challenges and Strategies in Development of Low-Dose Drug Products 10\u003c\/p\u003e \u003cp\u003e1.3 Summary 20\u003c\/p\u003e \u003cp\u003eAcknowledgments 20\u003c\/p\u003e \u003cp\u003eReferences 20\u003c\/p\u003e \u003cp\u003e\u003cb\u003eI Challenges and Strategies In Formulation Development of Oral Low-Dose Drug Products 23\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Challenges and Strategies In Formulation Development of Oral Solid Low-Dose Drug Products 25\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eJack Y. Zheng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 25\u003c\/p\u003e \u003cp\u003e2.2 Current Regulatory Environment and its Impact on New Drug Product Development 28\u003c\/p\u003e \u003cp\u003e2.3 Challenges in Developing Low-Dose Formulations 31\u003c\/p\u003e \u003cp\u003e2.4 Manufacturing Platforms for Low-Dose Drug Products 38\u003c\/p\u003e \u003cp\u003e2.5 Use of Experimental Design in Formulation and Process Development 42\u003c\/p\u003e \u003cp\u003e2.6 Containments 44\u003c\/p\u003e \u003cp\u003e2.7 Summary 45\u003c\/p\u003e \u003cp\u003eAcknowledgments 46\u003c\/p\u003e \u003cp\u003eReferences 46\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Particle Size of Drug Substance and Product Content Uniformity—Theoretical Considerations 49\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eKevin C. Johnson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 49\u003c\/p\u003e \u003cp\u003e3.2 Concept of Ideal Mixing 50\u003c\/p\u003e \u003cp\u003e3.3 Ideal Mixing Model Comparison with the Yalkowsky and Bolton Approach 56\u003c\/p\u003e \u003cp\u003e3.4 Experimental Support of Model Assumptions 59\u003c\/p\u003e \u003cp\u003e3.5 Analytical and Practical Considerations 61\u003c\/p\u003e \u003cp\u003eReferences 62\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Development of Low-Dose Formulations Using Fluidized Bed Granulation 63\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eJ. Joe Zhou and Ralph Lipp\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 63\u003c\/p\u003e \u003cp\u003e4.2 Granulation Fundamentals 66\u003c\/p\u003e \u003cp\u003e4.3 Theory of Fluidization 68\u003c\/p\u003e \u003cp\u003e4.4 Formulation Development 72\u003c\/p\u003e \u003cp\u003e4.5 Process Development 77\u003c\/p\u003e \u003cp\u003e4.6 Summary 86\u003c\/p\u003e \u003cp\u003eReferences 86\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Development of Low-Dose Solid Oral Formulations Using Wet Granulation 89\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eAhmad Almaya\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 89\u003c\/p\u003e \u003cp\u003e5.2 Granulation Mechanisms 91\u003c\/p\u003e \u003cp\u003e5.3 General Considerations on Wet Granulation 93\u003c\/p\u003e \u003cp\u003e5.4 Advantages and Disadvantages of Wet Granulation 100\u003c\/p\u003e \u003cp\u003e5.5 Use of Wet Granulation for Low-Dose Formulations 101\u003c\/p\u003e \u003cp\u003e5.6 Process-Induced Form Changes in Wet Granulation 109\u003c\/p\u003e \u003cp\u003e5.7 Concluding Remarks 111\u003c\/p\u003e \u003cp\u003eReferences 112\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Challenges In Development and Scale-Up of Low-Dose Drug Products By Dry Granulation: A Case Study 117\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMary T. Am Ende, Daniel O. Blackwood, Daniel S. Gierer, and Christopher P. Neu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 117\u003c\/p\u003e \u003cp\u003e6.2 Dry Granulation Process—Pros and Cons 118\u003c\/p\u003e \u003cp\u003e6.3 Overview of Dry Granulation Processes and Equipment Design 119\u003c\/p\u003e \u003cp\u003e6.4 Challenges for Low-Dose Product Development and their Assessment Methods 125\u003c\/p\u003e \u003cp\u003e6.5 Case Study: Formulation Challenges for Low-Dose Products 128\u003c\/p\u003e \u003cp\u003e6.6 Process Challenges During Dry Granulation Optimization for Low-Dose Products 140\u003c\/p\u003e \u003cp\u003e6.7 Conclusions 154\u003c\/p\u003e \u003cp\u003eAcknowledgments 155\u003c\/p\u003e \u003cp\u003eReferences 155\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Development of Low-Dose Solid Oral Tablets Using Direct Compression 159\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eJack Y. Zheng and Robert L. Ternik\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 159\u003c\/p\u003e \u003cp\u003e7.2 Advantages of Direct Compression 160\u003c\/p\u003e \u003cp\u003e7.3 Challenges in Low-Dose Tablet Development Using Direct Compression 162\u003c\/p\u003e \u003cp\u003e7.4 Formulation Development for Low-Dose Drug Products Using Direct Compression 169\u003c\/p\u003e \u003cp\u003e7.5 Manufacturing Process Development for Low-Dose Drug Products 187\u003c\/p\u003e \u003cp\u003e7.6 Scale-Up for Blending Operation 196\u003c\/p\u003e \u003cp\u003e7.7 Formulation Examples for Direct Compression 197\u003c\/p\u003e \u003cp\u003e7.8 Conclusions 199\u003c\/p\u003e \u003cp\u003eAcknowledgments 199\u003c\/p\u003e \u003cp\u003eReferences 200\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Reduction of Particle Size of Drug Substance For Low-Dose Drug Products 205\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eChristopher L. Burcham, Paul C. Collins, Daniel J. Jarmer, and Kevin D. Seibert\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 205\u003c\/p\u003e \u003cp\u003e8.2 Reduction of Particle Size of Drug Substance by Milling Technologies 207\u003c\/p\u003e \u003cp\u003e8.3 Reduction of Particle Size of Drug Substance Using Crystallization Technologies 216\u003c\/p\u003e \u003cp\u003e8.4 Scale-Up Considerations 218\u003c\/p\u003e \u003cp\u003e8.5 Emerging Technologies and Future Directions 219\u003c\/p\u003e \u003cp\u003eAcknowledgments 219\u003c\/p\u003e \u003cp\u003eReferences 219\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Function, Quality, and Regulations of Pharmaceutical Excipients For Oral Solid Dosage Forms 223\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eJack Y. Zheng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 223\u003c\/p\u003e \u003cp\u003e9.2 Classification of Pharmaceutical Excipients in Solid Dosage Forms 224\u003c\/p\u003e \u003cp\u003e9.3 Physicochemical Attributes of Pharmaceutical Excipients 225\u003c\/p\u003e \u003cp\u003e9.4 Regulatory Status and Excipient Quality 228\u003c\/p\u003e \u003cp\u003e9.5 Summary 235\u003c\/p\u003e \u003cp\u003eAcknowledgments 235\u003c\/p\u003e \u003cp\u003eReferences 236\u003c\/p\u003e \u003cp\u003e\u003cb\u003eII Challenges In Analytical Method Development For Oral Low-Dose Drug Products 239\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Analytical Method Development: Challenges and Solutions For Low-Dose Oral Dosage Forms 241\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eBeverly Nickerson, Reena M. Joseph, Charles Palmer, Alex M. Opio, and George H. Beresford\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 241\u003c\/p\u003e \u003cp\u003e10.2 Case Study 1: Drug Adsorption to Surfaces 242\u003c\/p\u003e \u003cp\u003e10.3 Case Study 2: Challenges Due to Nondrug-Related Impurities 245\u003c\/p\u003e \u003cp\u003e10.4 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\u003c\/p\u003e \u003cp\u003e10.5 Case Study 4: Small Volume Dissolution Testing 255\u003c\/p\u003e \u003cp\u003e10.6 Summary 261\u003c\/p\u003e \u003cp\u003eAcknowledgments 261\u003c\/p\u003e \u003cp\u003eReferences 261\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 In Vitro Dissolution Testing and Method Development 265\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eVivian A. Gray, Jack Y. Zheng, and Norman N. Sesi\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 265\u003c\/p\u003e \u003cp\u003e11.2 Overview of Dissolution Testing 265\u003c\/p\u003e \u003cp\u003e11.3 Dissolution Method Development 271\u003c\/p\u003e \u003cp\u003e11.4 Dissolution Method Development for Low-Dose Oral Drug Products 275\u003c\/p\u003e \u003cp\u003e11.5 Summary 279\u003c\/p\u003e \u003cp\u003eReferences 280\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Analysis of Physical Transformation of Api During Manufacture and Storage 283\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eGregory A. Stephenson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 283\u003c\/p\u003e \u003cp\u003e12.2 Discussion of Solid-State Forms 284\u003c\/p\u003e \u003cp\u003e12.3 Monitoring Processing Steps 285\u003c\/p\u003e \u003cp\u003e12.4 Measuring Transitions and Solid-Form Transformations in the Low-Dose Tablet 287\u003c\/p\u003e \u003cp\u003e12.5 Common Methods Used for Examination of Solid Forms 289\u003c\/p\u003e \u003cp\u003e12.6 Conclusions 305\u003c\/p\u003e \u003cp\u003eReferences 306\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 Physical Characterization Tests For Drug Substances Used In Low-Dose Formulations 309\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eRonald G. Iacocca\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 General Issues in the Physical Characterization of Micronized Powders Used in Low-Dose Formulations 309\u003c\/p\u003e \u003cp\u003e13.2 Particle Size Analysis 309\u003c\/p\u003e \u003cp\u003e13.3 Specific Surface Area Analysis 320\u003c\/p\u003e \u003cp\u003e13.4 Summary 323\u003c\/p\u003e \u003cp\u003eReferences 323\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 An Excipient Library Approach To Analytical Development For Low-Dose, Solid Oral Dosage Form Drug Products 327\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eQing Chang, Lisheng Kang, Keri Varner, Joyce Bridges, Norman Sesi, and Margo Palmieri\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 327\u003c\/p\u003e \u003cp\u003e14.2 Importance of Excipient Absorbance Background to Low-Dose Impurity Analysis 328\u003c\/p\u003e \u003cp\u003e14.3 Factors Affecting Excipient Absorbance Background 332\u003c\/p\u003e \u003cp\u003e14.4 Use of Excipient Library 339\u003c\/p\u003e \u003cp\u003e14.5 Conclusions 341\u003c\/p\u003e \u003cp\u003eAcknowledgments 341\u003c\/p\u003e \u003cp\u003eReferences 342\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Cleaning Verification For Highly Potent Compounds 345\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eBrian W. Pack\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 345\u003c\/p\u003e \u003cp\u003e15.2 Cleaning Validation vs Cleaning Verification 346\u003c\/p\u003e \u003cp\u003e15.3 Acceptance Limit Calculations 347\u003c\/p\u003e \u003cp\u003e15.4 Analytical Method Validation 352\u003c\/p\u003e \u003cp\u003e15.5 General Analytical Techniques 361\u003c\/p\u003e \u003cp\u003e15.6 Analytical Techniques for Low-Dose Compounds 364\u003c\/p\u003e \u003cp\u003e15.7 Conclusions 376\u003c\/p\u003e \u003cp\u003eAcknowledgments 377\u003c\/p\u003e \u003cp\u003eReferences 377\u003c\/p\u003e \u003cp\u003e\u003cb\u003eIII Containment Techniques For Highly Potent Pharmaceutical Compounds 381\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 Containment Challenges and Strategies For Potent Compounds In The Pharmaceutical Industry 383\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eVictoria Cathcart, Sarah Jones, and Beverly Nickerson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 383\u003c\/p\u003e \u003cp\u003e16.2 Safe Exposure Control Levels—Bands, Limits, and Handling Guidance 384\u003c\/p\u003e \u003cp\u003e16.3 The Hierarchy of Workplace Controls 389\u003c\/p\u003e \u003cp\u003e16.4 Case Studies 397\u003c\/p\u003e \u003cp\u003e16.5 Summary 403\u003c\/p\u003e \u003cp\u003eAcknowledgments 403\u003c\/p\u003e \u003cp\u003eReferences 403\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17 Sample Handling and Containment In Analytical Testing Laboratories 405\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eDavid S. Pattavina, Nancy Sage, and Beverly Nickerson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction 405\u003c\/p\u003e \u003cp\u003e17.2 Sample Handling Considerations 406\u003c\/p\u003e \u003cp\u003e17.3 Handling Potent Compounds in Standard Analytical Laboratories 407\u003c\/p\u003e \u003cp\u003e17.4 Handling Potent Compounds in a Containment Laboratory 411\u003c\/p\u003e \u003cp\u003e17.5 Additional Considerations for Handling Potent Materials 426\u003c\/p\u003e \u003cp\u003e17.6 Summary 427                                                                                                                                               \u003c\/p\u003e \u003cp\u003eAcknowledgments 428\u003c\/p\u003e \u003cp\u003eReferences 428\u003c\/p\u003e \u003cp\u003e\u003cb\u003eIV Regulatory Considerations In The Development of Low-Dose Drug Products 429\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18 Regulatory Considerations In The Development of Low-Dose Solid Oral Drug Products 431\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eRavi S. Harapanhalli\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction and Overview 431\u003c\/p\u003e \u003cp\u003e18.2 Three-Pronged Approach to Low-Dose Formulations 433\u003c\/p\u003e \u003cp\u003e18.3 Pharmaceutical Development Report 434\u003c\/p\u003e \u003cp\u003e18.4 Facility Controls for Highly Potent Drugs 451\u003c\/p\u003e \u003cp\u003e18.5 Conclusion 452\u003c\/p\u003e \u003cp\u003eReferences 453\u003c\/p\u003e \u003cp\u003eIndex 455\u003c\/p\u003e \u003cb\u003eJack Zheng, PhD,\u003c\/b\u003e is Research Advisor and Team Leader in the Pharmaceutical Sciences R\u0026amp;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.  Tested-and-proven strategies for developing and manufacturing low-dose oral drug products  \u003cp\u003eDeveloping and commercializing a low-dose oral drug product presents a number of hurdles that can quickly offset the drug's benefits. Written by a team of leading scientists in drug development, this book collects and synthesizes the knowledge, techniques, and strategies needed for developing low-dose drugs successfully. With this book's practical support, readers can overcome the hurdles at all stages in drug development, from formulation to manufacturing and control to regulatory compliance.\u003c\/p\u003e \u003cp\u003eFollowing an overview of the drug discovery and development process, the book is divided into four parts:\u003c\/p\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e\u003cb\u003ePart One\u003c\/b\u003e examines formulation and process development of low-dose drugs, including theoretical considerations concerning the particle size of the drug substance and content uniformity, micronization of the drug substance, and manufacturing platform technologies.\u003c\/p\u003e \u003c\/li\u003e \u003cli\u003e \u003cp\u003e\u003cb\u003ePart Two\u003c\/b\u003e focuses on challenges in analytical method development, including analytical control strategy, physical characterization of the micronized powder and the solid state of the active pharmaceutical ingredient in dosage forms, and cleaning verification of manufacturing equipment.\u003c\/p\u003e \u003c\/li\u003e \u003cli\u003e \u003cp\u003e\u003cb\u003ePart Three\u003c\/b\u003e investigates containment technologies used in analytical laboratories and manufacturing plants.\u003c\/p\u003e \u003c\/li\u003e \u003cli\u003e \u003cp\u003e\u003cb\u003ePart Four\u003c\/b\u003e deals with important regulatory considerations.\u003c\/p\u003e \u003c\/li\u003e \u003c\/ul\u003e \u003cp\u003eReaders learn how a variety of analytical methodologies are used in low-dose drug development, including dissolution testing, NMR, HPLC, and X-ray diffraction. Moreover, the book explains several possible manufacturing techniques, such as wet granulation, roller compaction, and direct compression alongside containment technologies for highly potent drugs. Case studies throughout the book demonstrate how particular strategies and techniques are applied in practice.\u003c\/p\u003e \u003cp\u003ePharmaceutical scientists as well as students will find overcoming the obstacles in developing low-dose drug products much easier when they have this book on hand to consult at all stages in the drug development and manufacturing process.\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47989235548389,"sku":"NP9780470056097","price":156.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9780470056097.jpg?v=1761783318","url":"https:\/\/k12savings.com\/products\/formulation-and-analytical-development-for-low-dose-oral-drug-products-isbn-9780470056097","provider":"K12savings","version":"1.0","type":"link"}