Formulation and Analytical Development for Low-Dose Oral Drug Products / Edition 1

Hardcover (Print)
Buy New
Buy New from
Used and New from Other Sellers
Used and New from Other Sellers
from $103.55
Usually ships in 1-2 business days
(Save 23%)
Other sellers (Hardcover)
  • All (7) from $103.55   
  • New (5) from $103.55   
  • Used (2) from $104.87   


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.

Read More Show Less

Editorial Reviews

Doody's Review Service
Reviewer: Joseph Boullata, PharmD (University of Pennsylvania School of Nursing)
Description: This welcome addition to books on dosage formulations has as its focus the challenging issue of developing and bringing to market oral drug products containing a low dose (< 1 mg) of active ingredient. These include widely used products such as oral contraceptives and thyroid hormone replacement.
Purpose: The objective is to provide a concise review of the development of low-dose drug products from pharmaceutical, analytical, and regulatory perspectives.
Audience: This book is written primarily for formulation scientists, analytical scientists, and regulatory specialists who will deal with low-dose oral drug products in industry or academia, as well as graduate students and postdoctoral fellows preparing for the field.
Features: Following an excellent overview chapter by the editor, the book is divided into four sections. The first section on formulation development provides detailed information on strategies dealing with particle size and process methods issues. The second section discusses analytical methods for low dose products given the challenges of such low quantities of active ingredient. The third section has two chapters on technology for containment related to the potency of the active ingredient. The last section includes a final chapter on regulatory considerations. Among the book's outstanding features are 97 tables, 74 figures, some color plates, and dozens of equations. Numerous formulation case studies are provided. The referencing format is not consistent across the chapters, but the 7-page index appears to be adequate. The contributors come predominantly from industry, and it is unfortunate not to have more from academia and regulatory bodies.
Assessment: This book is unique in its depth of coverage of the topic.
Read More Show Less

Product Details

  • ISBN-13: 9780470056097
  • Publisher: Wiley
  • Publication date: 1/27/2009
  • Edition description: New Edition
  • Edition number: 1
  • Pages: 465
  • Product dimensions: 6.50 (w) x 9.60 (h) x 0.90 (d)

Meet the Author

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.

Read More Show Less

Table of Contents




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.




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.



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.


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.


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.


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.



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.



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.



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.




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.



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.


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.


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.


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.



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.




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.



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.




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.



Read More Show Less

Customer Reviews

Be the first to write a review
( 0 )
Rating Distribution

5 Star


4 Star


3 Star


2 Star


1 Star


Your Rating:

Your Name: Create a Pen Name or

Barnes & Review Rules

Our reader reviews allow you to share your comments on titles you liked, or didn't, with others. By submitting an online review, you are representing to Barnes & that all information contained in your review is original and accurate in all respects, and that the submission of such content by you and the posting of such content by Barnes & does not and will not violate the rights of any third party. Please follow the rules below to help ensure that your review can be posted.

Reviews by Our Customers Under the Age of 13

We highly value and respect everyone's opinion concerning the titles we offer. However, we cannot allow persons under the age of 13 to have accounts at or to post customer reviews. Please see our Terms of Use for more details.

What to exclude from your review:

Please do not write about reviews, commentary, or information posted on the product page. If you see any errors in the information on the product page, please send us an email.

Reviews should not contain any of the following:

  • - HTML tags, profanity, obscenities, vulgarities, or comments that defame anyone
  • - Time-sensitive information such as tour dates, signings, lectures, etc.
  • - Single-word reviews. Other people will read your review to discover why you liked or didn't like the title. Be descriptive.
  • - Comments focusing on the author or that may ruin the ending for others
  • - Phone numbers, addresses, URLs
  • - Pricing and availability information or alternative ordering information
  • - Advertisements or commercial solicitation


  • - By submitting a review, you grant to Barnes & and its sublicensees the royalty-free, perpetual, irrevocable right and license to use the review in accordance with the Barnes & Terms of Use.
  • - Barnes & reserves the right not to post any review -- particularly those that do not follow the terms and conditions of these Rules. Barnes & also reserves the right to remove any review at any time without notice.
  • - See Terms of Use for other conditions and disclaimers.
Search for Products You'd Like to Recommend

Recommend other products that relate to your review. Just search for them below and share!

Create a Pen Name

Your Pen Name is your unique identity on It will appear on the reviews you write and other website activities. Your Pen Name cannot be edited, changed or deleted once submitted.

Your Pen Name can be any combination of alphanumeric characters (plus - and _), and must be at least two characters long.

Continue Anonymously

    If you find inappropriate content, please report it to Barnes & Noble
    Why is this product inappropriate?
    Comments (optional)