Pharmaceutical Dosage forms:

Parenteral Medications Volume 1

Second Edition, Revised and Expanded

Edited by Kenneth E. Avis

The University of Tennessee Memphis, Tennessee

Herbert A. Lieberman
H.H. Lieberman Associates, Inc. Consultant Services Livingston, New Jersey

Leon Ladiman
Lachman Consultant Services Westbury, New York

Marcel Dekker, Inc.

New York Basel Hong Kong

Contents

Preface Contributors Contents of Pharmaceutical Dosage Forms: Parenteral Medications, Second Edition, Revised and Expanded, Volumes 2 and 3 Contents of Pharmaceutical Dosage Forms: Tablets, Second Edition, Revised and Expanded, Volumes 1-3 Contents of Pharmaceutical Dosage Forms: Disperse Systems, Volumes 1 and 2 Chapter 1 The Parenteral Dosage Form and Its Historical Development Kenneth E. Avis I. The Dosage Form II. History of Parenteral Medications Appendix A: Glossary of Terms Appendix B: Highlights in the History of Parenteral Medications References Chapter 2 Parenteral Drug Administration: Routes, Precautions, Problems, Complications, and Drug Delivery Systems Richard J. Duma, Michael J. Akers, and Salvatore J. Turco I. II. III. IV. Introduction General Indications for Parenteral Administration of Drugs Pharmaceutical Factors Affecting Parenteral Administration Specific Routes of Administration Distribution of Parenterally Administered Agents

in xi
xiii

1 1 4 12 14 15

17

17 18 19 21 39

vii

Contents Precautions, Problems, Hazards, and Complications Associated with Parenteral Drug Administration Methods and Devices for Drug Delivery Systems Summary References

VI. VII.

41 49 56 57

Chapter 3

Biopharmaceutics of Injectable Medications Sol Mo tola I. II. Introduction Physicochemical and Physiological Factors Affecting Drug Absorption by Injection: An Overview Application of Pharmacokinetics to Biopharmaceutic Investigations: Pharmacokinetic Models Examples of Biopharmaceutic /Pharmacokinetic Principles Regulatory Considerations for Bioequivalence Studies Bioequivalence Study of Two Injectable Forms of t h e Same Drug Summary References

59

59

60 77 98 108 109 111 112

III. IV. V. VI. VII.

Chapter 4

Preformulation Research of Parenteral Medications Sol Motola and Shreeram N. I. II. III. IV. V. VI. VII. VIII. Agharkar

115

Introduction Drug Substance Physicochemical Properties Accelerated Stability Evaluation General Modes of Drug Degradation Preformulation Studies for Proteins and Peptides Preformulation Screening of Parenteral Packaging Components Summary Preformulation Worksheet References

115 116 140 150 154 158 163 163 169

Chapter 5

Formulation of Small Volume Parenterals

173
173 174 227 234 244 245

Patrick P. DeLuca and James C. Boylan I. II. III. IV. V. Introduction Formulation Principles Container Effects on Formulation Stability Evaluation Process Effects References

Contents Chapter 6 Formulation of Large Volume Parenterals Levit J. Demorest and Jeffrey G. Hamilton I. II. III. IV. V. Introduction Concepts of Formulation Formulation Development Solution Quality Summary References
249 250 273 280 281 281

249

Chapter 7

Parenteral Products of Peptides and Proteins Yu-Chang John Wang I. II. III. IV. V. Introduction Characteristics of Proteins and Peptides Formulation Principles Compatibility with Packaging Components and Infusion Sets Formulation of Market Products References

283

283 284 302 310 312 317

Chapter 8

Sterile Diagnostics Leif E. Olsen I. II. III. IV. V. VI. VII. Introduction Diagnostic Products Defined Sterile Diagnostics Definitions Aseptic Manufacturing Considerations Validation Program Conclusion References

321

321 321 322 325 330 351 359 359

Chapter 9

Glass Containers for Parenterals R. Paul Abendroth and Robert N. Clark

I. II.

361

III.
IV. V. VI.

VII. VIII.

Introduction The Nature of Glass United States Pharmacopeia Glassware Classifications The Manufacture of Glass Containers Chemical Performance Mechanical Performance The Container and Closure as a System Quality Assurance References

361 361 362 369 375 380 380 382 384

Contents Chapter 10 Use of Plastics for Parenteral Packaging John M. Anes, Robert S. Nase, and Charles H. White I. II. III. IV. V. VI. Introduction Fundamentals Fabrication Processes Important Criteria for Selection of Plastics Plastics Used in Parenteral Packaging Quality Assurance of Parenteral Containers References 387 389 398 407 422 439 443 387

Chapter 11 Elastomeric Closures for Parenterals Edward J. Smith and Robert J. Nash I. II. III. IV. V. VI. VII. VIII. IX. X. XI. Elastomeric Parenteral Packaging Components: A Physical Description Physical Description of Rubber Types of Rubber Used in Parenteral Packaging Closure Design Rubber Compounding Vulcanization Process Closure Manufacture and Control Closure Design Qualification Regulatory Considerations Interaction of Drug Formulations with Rubber Closures Contemporary Closure-Related Issues References

445

445 450 451 462 463 470 477 494 503 505 507 508

Chapter 12 Parenteral Products in Hospital and Home Care Pharmacy Practice John W. Levchuk Introduction The Preparation of Sterile Dosage Forms in the Hospital and in Home Care III. Dispensing and Compounding Processes IV. Technology of Sterile Compounding in the Hospital Pharmacy V. Clinical Supply and Use of Sterile Products VI. Quality Assurance VII. Conclusion Appendix: Abbreviated Sequence for Preparing a Series of Extemporaneously Compounded I.V. Admixtures References Index I. II. 513 513 524 532 547 552 562 513

563 566 569