Formulation and Analytical Development for Low-Dose Oral Drug Products

Ed.: Zheng, Jack

• Gebundenes Buch

Produktbeschreibung

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.

Produktdetails

• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 496
• Erscheinungstermin: 1. Februar 2009
• Englisch
• Abmessung: 241mm x 159mm x 30mm
• Gewicht: 790g
• ISBN-13: 9780470056097
• ISBN-10: 0470056096
• Artikelnr.: 25059708

Autorenporträt

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.

Inhaltsangabe

Preface. Foreword. Contributors. 1. An Overview (Jack Y. Zheng). 1.1 The
Drug Discovery and Development Process. 1.2 Challenges and Strategies in
Development of Low-Dose Drug Products. 1.3 Summary. Acknowledgments.
References. PART I: CHALLENGES AND STRATEGIES IN FORMULATION DEVELOPMENT OF
ORAL LOW-DOSE DRUG PRODUCTS. 2. Challenges and Strategies in Formulation
Development of Oral Solid Low-Dose Drug Products (Jack Y. Zheng). 2.1
Introduction. 2.2 Current Regulatory Environment and Its Impact on New Drug
Product Development. 2.3 Challenges in Developing Low-Dose Formulations.
2.4 Manufacturing Platforms for Low-Dose Drug Products. 2.5 Use of
Experimental Design in Formulation and Process Development. 2.6
Containments. 2.7 Summary. Acknowledgments. References. 3. Particle Size of
Drug Substance and Product Content Uniformity - Theoretical Considerations
(Kevin C. Johnson). 3.1 Introduction. 3.2 Concept of Ideal Mixing. 3.3
Ideal Mixing Model Comparison with the Yalkowsky and Bolton Approach. 3.4
Experimental Support of Model Assumptions. 3.5 Analytical and Practical
Considerations. References. 4. Development of Low-Dose Formulations Using
Fluidized Bed Granulation (J. Joe Zhou and Ralph Lipp). 4.1 Introduction.
4.2 Granulation Fundamentals. 4.3 Theory of Fluidization. 4.4 Formulation
Development. 4.5 Process Development. 4.6 Summay. References. 5.
Development of Low-Dose Solid Oral Formulations Using Wet Granulation
(Ahmad Almaya). 5.1 Introduction. 5.2 Granulation Mechanisms. 5.3 General
Considerations on Wet Granulation. 5.4 Advantages and Disadvantages of Wet
Granulation. 5.5 Use of Wet Granulation for Low-Dose Formulations. 5.6
Process-Induced Form Changes in Wet Granulation. 5.7 Concluding Remarks.
References. 6. Challenges in Development and Scale-Up of Low Dose Drug
Products by Dry Granulation: A Case Study (Mary T. Am Ende, Daniel O.
Blackwood, Daniel S. Gierer, and Christopher P. Neu). 6.1 Introduction. 6.2
Dry Granulation Process - Pros and Cons. 6.3 Overview of Dry Granulation
Processes and Equipment Design. 6.4 Challenges for Low-Dose Product
Development and their Assessment Methods. 6.5 Case Study: Formulation
Challenges for Low-Dose Products. 6.6 Process Challenges During Dry
Granulation Optimization for Low-Dose Products. 6.7 Conclusions.
Acknowledgments. References. 7. Development of Low-Dose Solid Oral Tablets
Using Direct Compression (Jack Y. Zheng and Robert L. Ternik). 7.1
Introduction. 7.2 Advantages of Direct Compression. 7.3 Challenges in
Low-Dose Tablet Development Using Direct Compression. 7.4 Formulation
Development for Low-Dose Drug Products Using Direct Compression. 7.5
Manufacturing Process Development for Low-Dose Drug Products. 7.6 Scale-Up
for Blending Operation. 7.7 Formulation Examples for Direct Compression.
7.8 Conclusions. Acknowledgments. References. 8 Reduction of Particle Size
of Drug Substance for Low-Dose Drug Products (Christopher L. Burcham, Paul
C. Collins, Daniel J. Jarmer, and Kevin D. Seibert). 8.1 Introduction. 8.2
Reduction of Particle Size of Drug Substance by Milling Technologies. 8.3
Reduction of Particle Size of Drug Substance Using Crystallization
Technologies. 8.4 Scale-Up Considerations. 8.5 Emerging Technologies and
Future Directions. Acknowledgments. References. 9. Function, Quality, and
Regulations of Pharmaceutical Excipients for Oral Solid Dosage Forms (Jack
Y. Zheng). 9.1 Introduction. 9.2 Classification of Pharmaceutical
Excipients in Solid Dosage Forms. 9.3 Physicochemical Attributes of
Pharmaceutical Excipients. 9.4 Regulatory Status and Excipient Quality. 9.5
Summary. Acknowledgments. References. PART II: CHALLENGES IN ANALYTICAL
METHOD DEVELOPMENT FOR ORAL LOW-DOSE DRUG PRODUCTS. 10. Analytical Method
Development: Challenges and Solutions for Low-Dose Oral Dosage Forms
(Beverly Nickerson, Reena M. Joseph, Charles Palmer and Alex M. Opio and
George H. Beresford). 10.1 Introduction. 10.2 Case Study 1: Drug Adsorption
to Surfaces. 10.3 Case Study 2: Challenges Due to Nondrug-Related
Impurities. 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. 10.5 Case Study 4: Small Volume Dissolution
Testing. 10.6 Summary. Acknowledgments. References. 11. In Vitro
Dissolution Testing and Method Development (Vivian A. Gray Jack Y. Zheng
and Norman N. Sesi). 11.1 Introduction. 11.2 Overview of Dissolution
Testing. 11.3 Dissolution Method Development. 11.4 Dissolution Method
Development for Low-Dose Oral Drug Products. 11.5 Summary. References. 12.
Analysis of Physical Transformation of API During Manufacture and Storage
(Gregory A. Stephenson). 12.1 Introduction. 12.2 Discussion of Solid-State
Forms. 12.3 Monitoring Processing Steps. 12.4 Measuring Transitions and
Solid-Form Transformations in the Low-Dose Tablet. 12.5 Common Methods Used
for Examination of Solid Forms. 12.6 Conclusions. References. 13. Physical
Characterization Tests for Drug Substances Used in Low-Dose Formulations
(Ronald G. Iacocca). 13.1 General Issues in the Physical Characterization
of Micronized Powders Used in Low-Dose Formulations. 13.2 Particle Size
Analysis. 13.3 Specific Surface Area Analysis. 13.4 Summary. References.
14. An Excipient Library Approach to Analytical Development for Low-Dose,
Solid Oral Dosage Form Drug Products (Qing Chang, Lisheng Kang, Keri
Varner, Joyce Bridges, Norman Sesi, and Margo Palmieri). 14.1 Introduction.
14.2 Importance of Excipient Absorbance Background to Low-Dose Impurity
Analysis. 14.3 Factors Affecting Excipient Absorbance Background. 14.4 Use
of Excipient Library. 14.5 Conclusions. Acknowledgments. References. 15.
Cleaning Verification for Highly Potent Compounds (Brian W. Pack). 15.1
Introduction. 15.2 Cleaning Validation vs Cleaning Verification. 15.3
Acceptance Limit Calculations. 15.4 Analytical Method Validation. 15.5
General Analytical Techniques. 15.6 Analytical Techniques for Low-Dose
Compounds. 15.7 Conclusions. Acknowledgments. References. PART III:
CONTAINMENT TECHNIQUES FOR HIGHLY POTENT PHARMACEUTICAL COMPOUNDS. 16
Containment Challenges and Strategies for Potent Compounds in the
Pharmaceutical Industry (Victoria Cathcart, Sarah Jones, Beverly
Nickerson). 16.1 Introduction. 16.2 Safe Exposure Control Levels-Bands,
Limits, and Handling Guidance. 16.3 The Hierarchy of Workplace Controls.
16.4 Case Studies. 16.5 Summary. Acknowledgments. References. 17. Sample
Handling and Containment in Analytical Testing Laboratories (David
Pattavina, Nancy Sage, and Beverly Nickerson). 17.1 Introduction. 17.2
Sample Handling Considerations. 17.3 Handling Potent Compounds in Standard
Analytical Laboratories. 17.4 Handling Potent Compounds in a Containment
Laboratory. 17.5 Additional Considerations for Handling Potent Materials.
17.6 Summary. Acknowledgments. References. PART IV: REGULATORY
CONSIDERATIONS IN THE DEVELOPMENT OF LOW-DOSE DRUG PRODUCTS. 18. Regulatory
Considerations in the Development of Low-Dose Solid Oral Drug Products
(Ravi S. Harapanhalli). 18.1 Introduction and Overview. 18.2 Three-Pronged
Approach to Low-Dose Formulations. 18.3 Pharmaceutical Development Report.
18.4 Facility Controls for Highly Potent Drugs. 18.5 Conclusion.
References. Index.