Bret Berner - Drug Delivery Approaches: Perspectives from Pharmacokinetics and Pharmacodynamics

1. Chapter 1
2. Chapter 2
3. Chapter 3
4. Chapter 4
5. Chapter 5
6. Chapter 6
7. Chapter 7
8. Chapter 8
9. Chapter 9
10. Chapter 10

1. Chapter 1
2. Chapter 2
3. Chapter 3
4. Chapter 4
5. Chapter 5
6. Chapter 6
7. Chapter 7
8. Chapter 8
9. Chapter 9
10. Chapter 10
11. Chapter 11
12. Chapter 12

Edited by

Bret Berner
Seattle, WA, USA

Toufigh Gordi
South San Francisco, California, USA

Heather A. E. Benson
Curtin University of Technology, School of Pharmacy, Perth, Australia

Michael S. Roberts
University of Queensland, School of Medicine, Brisbane, Australia

This edition first published 2021
2021 by John Wiley & Sons, Inc.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

The right of Bret Berner, Toufigh Gordi, Heather A. E. Benson, and Michael S. Roberts to be identified as the editors of this work has been asserted in accordance with law.

Registered Office
John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA

Editorial Office
111 River Street, Hoboken, NJ 07030, USA

For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.

Wiley also publishes its books in a variety of electronic formats and by printondemand. Some content that appears in standard print versions of this book may not be available in other formats.

Limit of Liability/Disclaimer of Warranty
In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

Library of Congress CataloginginPublication Data is applied for
Hardback ISBN: 9781119772736

Cover Design: Wiley
Cover Image: Peshkova/iStock/Getty Images

Drug delivery aims to enable appropriate drug absorption based on the physical and chemical properties, expected dose, and route of administration. For new chemical entities, drug delivery is initially expedient and adapts the dosage form of the active compound to the stage of development based on feedback from the iterative understanding of the pharmacokinetics ( PK ), pharmacodynamics ( PD ), and potential sources of variability of the candidate drug. In actual practice, the final formulation is often based at most on the determination of a dose response. Models combining physical and pharmacokinetic properties of a drug candidate with dissolution, in vivo studies, and known transporter and biomarkers have been shown to predict the time course of events successfully in vivo. To improve delivery of older chemical entities, whether controlled release, modified release, temporally or sitecontrolled delivery, development of a target pharmacokinetic profile to optimize efficacy for duration and/or to reduce adverse events is the starting and ending point for designing a dosage form.

This book discusses the options for drug delivery within the available routes of administration to achieve the target profiles and approaches as defined by these models. It is intended for use by graduate students and novice and skilled practitioners, who are developing either new or repurposed drugs. In particular, this book should prove useful to pharmaceutical scientists and engineers, including formulators, pharmacokineticists, clinical pharmacologists, and those interested in the interaction of these disciplines.

This book begins with an appreciation of modeling of drug absorption and physiological effects and the use of pharmacokinetic and physiologically based models and follows with an introduction to physiologicalbased pharmacokinetics ( PBPK ). For the most common route of delivery, oral administration, there are chapters dealing with both PBPK and the multiplicity of options for oral drug delivery dosage forms. Endpoints that may substitute for measures of delivery or efficacy and rigorous skin permeation testing are discussed as targets for topical drug delivery and may have both development and regulatory applications. In the case of systemic transdermal delivery, understanding the pharmacokinetics of the formulation and the drug is essential to guide formulation from earliest conception throughout development. Separate chapters discuss the biological and delivery approaches to pulmonary and mucosal delivery. For emergency care settings, the relationship between parenteral infusion profiles and PK/PD is the key topic discussed. The book concludes with some more recent trends with chapters discussing virtual experiments to elucidate mechanisms and approaches to drug delivery and personalized medicine.

We would like to thank all the authors for their contributions to this book. We wish to especially thank our coeditors, Heather Benson and Michael Roberts, for conception, initiation, and review of this book and our editor at Wiley, Jonathan Rose, for his patience and support during the writing of this book.

May 30, 2020

Bret Berner, PhD
Seattle, WA
Toufigh Gordi, PhD
San Carlos, CA