Ten years ago, the first edition of Oral Drug Absorption was published with the intent of closing the gap between gastroenterology textbooks on the physiology of the gastrointestinal (GI) tract and pharmaceutical textbooks on oral drug formulations. In the ensuing years, the field of oral drug absorption has evolved significantly on several fronts. First, there has been acceptance and increasing implementation of the biopharmaceutics classification scheme (BCS) concept, both at the regulatory and drug development levels. Second, application of biorelevant media to better understand active pharmaceutical ingredient (API) behavior in the GI tract has become widespread, not only for solubility and dissolution, but also for permeability applications. Third, the role of transporters in drug uptake across the GI mucosa has been recognized and is under intensive investigation. The same applies to drug metabolism in the gut wall, and within the next decade, we should be able to quantitatively describe both of these phenomena as they relate to prediction of API bioavailability. Fourth, our understanding of GI hydrodynamics and the availability of fluid in the various segments of the GI tract is slowly but surely improving. Fifth, there is a very strong interest in applying physiologically based pharmacokinetic (PBPK) modeling to oral drug absorption; this has become possible with the advent of sophisticated software programs like GastroPlus1 and PK-Sim1 and will surely become one of our most powerful tools in the years to come. And last but not least, the quality by design paradigm has aroused interest in new techniques to better link the composition and manufacture of oral drug products with their in vivo performance.
As a result of all these developments, it is high time to bring out a second edition of Oral Drug Absorption that captures the rapid progress in the field. In this edition, we start out with a chapter on the fundamentals of GI physiology— as it relates to oral drug absorption—and in the first section, we describe several aspects in more detail in chapters specifically addressing absorption mechanisms, GI motility, gut wall metabolism, food effects, and drug absorption in children and various disease states. The second section focuses on the BCS and the impact it is making on pharmaceutical R&D and regulation of oral drug products. Additionally, separate chapters are devoted to the measurement and interpretation of the key BCS parameters, solubility and permeability. The third section, entitled ‘‘Nonclinical Methods to Evaluate Oral Formulations,’’ first describes appropriate dissolution tests to characterize formulations in preclinical development—be they intended for immediate or controlled release in the GI tract. Then state of the art practice for formulation screening and development in the industry is recounted for immediate release products and for controlled release products. This section is wrapped up by a chapter devoted to implementation of PBPK modeling at the preclinical level. The last section turns attention to bioequivalence studies. Increasingly, alternatives to human pharmacokinetic studies are being used to obtain approval of generic drug products and to obtain continued approval for existing products when changes have been made to the composition or method of manufacture. The section is introduced with a chapter providing the fundamentals and current status of bioavailability and bioequivalence. The application of BCS and in vitro–in vivo correlation (IVIVC) to the proof of bioequivalence is then described in separate chapters, and the evolution of regulations pertaining to bioequivalence is put into global perspective. In recognition of the increased interest in application of IVIVC for proof of bioequivalence, we have also provided a CD, which shows the user how to generate IVIVCs utilizing an Excel spreadsheet. Numerous examples are given to illustrate the underlying theory and show how the IVIVC works, and it is hoped that this CD will become an integral part of the toolbox used by pharmaceutical scientists to facilitate formulation design and optimization on a day-to-day basis.
Of course, producing a new edition of a textbook requires the assistance of many people, and Oral Drug Absorption is no exception. We wish to thank Sandy Beberman and Sherri Niziolek for their untiring enthusiasm and support of this project. We are also indebted to the authors for their splendid efforts in preparing chapters that reflect state-of-the-art thinking in oral drug absorption. We also wish to thank our families for their support and understanding that books are largely created in the evenings and on weekends. Finally, we thank the readers of the first edition for the excellent feedback and stimulus to produce an updated version.
- The Editors -
Contents
Part I: Physiology of Oral Drug Absorption
- 1. Physiological Factors Affecting Drug Release and Absorption in the Gastrointestinal Tract
- 2. Drug Transport Mechanisms Across the Intestinal Epithelium
- 3. Gastrointestinal Transit and Drug Absorption
- 4. Gut Wall Metabolism
- 5. Food Effects on Drug Absorption and Dosage Form Performance
- 6. Oral Drug Absorption in Pediatric Populations
- 7. Gastrointestinal Disease and Dosage Form Performance
Part II: The Biopharmaceutics Classification System
- 8. The Biopharmaceutics Classification System: Recent Applications in Pharmaceutical Discovery, Development, and Regulation
- 9. Drug Solubility in the Gastrointestinal Tract
- 10. Permeability Measurement
- 11. BCS: Today and Tomorrow
Part III: Nonclinical Methods to Evaluate Oral Formulations
- 12. Dissolution Testing to Forecast In Vivo Performance of Immediate-Release Formulations
- 13. Dissolution Testing to Forecast the In Vivo Performance of MR Formulations
- 14. Modified-Release Dosage Forms: Formulation Screening in the Pharmaceutical Industry
- 15. Immediate Release Oral Dosage Forms: Formulation Screening in the Pharmaceutical Industry
- 16. Computer Models for Predicting Drug Absorption
Part IV: Bioequivalence Studies
- 17. In Vivo Bioequivalence Assessment
- 18. Biowaiving Based on the BCS—A Global Comparison
- 19. Biowaiving Based on In Vitro-In Vivo Correlation
Appendix
Index
Product Details
- Hardcover: 450 pages
- Publisher: Informa Healthcare; 2 edition (January 15, 2010)
- Language: English
- ISBN-10: 1420077333
- ISBN-13: 978-1420077339
- Product Dimensions: 9 x 6.2 x 1.1 inches
List Price: $229.95