Pharmaceutical Manufacturing Handbook

This handbook features contributions from a team of expert authors representing the many disciplines within science, engineering, and technology that are involved in pharmaceutical manufacturing. They provide the information and tools you need to design, implement, operate, and troubleshoot a pharmaceutical manufacturing system. The editor, with more than thirty years' experience working with pharmaceutical and biotechnology companies, carefully reviewed all the chapters to ensure that each one is thorough, accurate, and clear.

Preface xiii

Section 1 Manufacturing Specialties 1

1.1 Biotechnology-Derived Drug Product Development 3
Stephen M. Carl, David J. Lindley, Gregory T. Knipp, Kenneth R. Morris, Erin Oliver, Gerald W. Becker, and Robert D. Arnold

1.2 Regulatory Considerations in Approval on Follow-On Protein Drug Products 33
Erin Oliver, Stephen M. Carl, Kenneth R. Morris, Gerald W. Becker, and Gregory T. Knipp

1.3 Radiopharmaceutical Manufacturing 59
Brit S. Farstad and Iván Peñuelas

Section 2 Aseptic Processing 97

2.1 Sterile Product Manufacturing 99
James Agalloco and James Akers

Section 3 Facility 137

3.1 From Pilot Plant to Manufacturing: Effect of Scale-Up on Operation of Jacketed Reactors 139
B. Wayne Bequette

3.2 Packaging and Labeling 159
Maria Inês Rocha Miritello Santoro and Anil Kumar Singh

3.3 Clean-Facility Design, Construction, and Maintenance Issues 201
Raymond K. Schneider

Section 4 Normal Dosage Forms 233

4.1 Solid Dosage Forms 235
Barbara R. Conway

4.2 Semisolid Dosages: Ointments, Creams, and Gels 267
Ravichandran Mahalingam, Xiaoling Li, and Bhaskara R. Jasti

4.3 Liquid Dosage Forms 313
Maria V. Rubio-Bonilla, Roberto Londono, and Arcesio Rubio

Section 5 New Dosage Forms 345

5.1 Controlled-Release Dosage Forms 347
Anil Kumar Anal

5.2 Progress in the Design of Biodegradable Polymer-Based Microspheres for Parenteral Controlled Delivery of Therapeutic Peptide/Protein 393
Shunmugaperumal Tamilvanan

5.3 Liposomes and Drug Delivery 443
Sophia G. Antimisiaris, Paraskevi Kallinteri, and Dimitrios G. Fatouros

5.4 Biodegradable Nanoparticles 535
Sudhir S. Chakravarthi and Dennis H. Robinson

5.5 Recombinant Saccharomyces cerevisiae as New Drug Delivery System to Gut: In Vitro Validation and Oral Formulation 565
Stéphanie Blanquet and Monique Alric

5.6 Nasal Delivery of Peptide and Nonpeptide Drugs 591
Chandan Thomas and Fakhrul Ahsan

5.7 Nasal Powder Drug Delivery 651
Jelena Filipović-Grčić and Anita Hafner

5.8 Aerosol Drug Delivery 683
Michael Hindle

5.9 Ocular Drug Delivery 729
Ilva D. Rupenthal and Raid G. Alany

5.10 Microemulsions as Drug Delivery Systems 769
Raid G. Alany and Jingyuan Wen

5.11 Transdermal Drug Delivery 793
C. Scott Asbill and Gary W. Bumgarner

5.12 Vaginal Drug Delivery 809
José das Neves, Maria Helena Amaral, and Maria Fernanda Bahia

Section 6 Tablet Production 879

6.1 Pharmaceutical Preformulation: Physicochemical Properties of Excipients and Powers and Tablet Characterization 881
Beom-Jin Lee

6.2 Role of Preformulation in Development of Solid Dosage Forms 933
Omathanu P. Perumal and Satheesh K. Podaralla

6.3 Tablet Design 977
Eddy Castellanos Gil, Isidoro Caraballo, and Bernard Bataille

6.4 Tablet Production Systems 1053
Katharina M. Picker-Freyer

6.5 Controlled Release of Drugs from Tablet Coatings 1099
Sacide Alsoy Altinkaya

6.6 Tablet Compression 1133
Helton M. M. Santos and João J. M. S. Sousa

6.7 Effects of Grinding in Pharmaceutical Tablet Production 1165
Gavin Andrews, David Jones, Hui Zhai, Osama Abu Diak, and Gavin Walker

6.8 Oral Extended-Release Formulations 1191
Anette Larsson, Susanna Abrahmsén-Alami, and Anne Juppo

Section 7 Role of Nanotechnology 1223

7.1 Cyclodextrin-Based Nanomaterials in Pharmaceutical Field 1225
Erem Bilensoy and A. Attila Hincal

7.2 Nanotechnology in Pharmaceutical Manufacturing 1249
Yiguang Jin

7.3 Pharmaceutical Nanosystems: Manufacture, Characterization, and Safety 1289
D. F. Chowdhury

7.4 Oil-in-Water Nanosized Emulsions: Medical Applications 1327
Shunmugaperumal Tamilvanan

Index 1367

SHAYNE COX GAD, PhD, DABT, ATS, is the Principal of Gad Consulting Services. Dr. Gad has more than thirty years of experience as a toxicologist, statistical consultant, manager, and general consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of twenty-nine books and numerous papers, presentations, and other publications. Everything you need to know to manufacture high-quality pharmaceuticals safely and efficiently

From the building of a facility to dosage and delivery forms to tablet production, this handbook covers the full range of topics to help you understand and apply the methods needed to manufacture drugs safely and efficiently. Thoroughly up to date, the handbook also examines the emerging role of nanotechnology in the development and manufacture of drugs and medical devices. Comprehensive in its presentation, this reference includes an entire section dedicated to the economics and business strategies of pharmaceutical manufacturing.

This handbook features contributions from a team of expert authors representing the manydisciplines within science, engineering, and technology that are involved in pharmaceutical manufacturing. They provide the information and tools you need to design, implement, operate,and troubleshoot a pharmaceutical manufacturing system. The editor, with more than thirty years' experience working with pharmaceutical and biotechnology companies, carefully reviewed all the chapters to ensure that each one is thorough, accurate, and clear.

Among the key topics covered are:

• Radiopharmaceutical manufacturing

• Clean facility design, construction, and maintenance

• Controlled-release dosage forms

• Biodegradable nanoparticles

• Tablet production systems

• Cyclodextrin-based nanomaterials in the pharmaceutical field

This publication serves as a hands-on reference for all scientists, engineers, and managers involved in pharmaceutical manufacturing, providing a basic primer for novices and detailing the latest discoveries and techniques for more experienced practitioners.