Physiological Pharmaceutics: Barriers to Drug Absorption / Edition 1

by Neena Washington, Clive Washington, Clive Wilson

Overview

In recent years, the emphasis in drug development has been the design of new delivery systems rather than new drugs. It is the aim of innovative pharmaceutical scientists to design the new dosage forms to overcome the body's barrier mechanisms which have specifically evolved to exclude foreign material.

This book provides an integrated approach to the study of drug formulation in the body with the emphasis on the formulation variables rather than the drugs. The link between physiology and pharmaceutics is presented to give an essential background of biological principles for the pharmacy student, pharmaceutical formulator and healthcare professional. Complex mathematical aspects of physical chemistry have been avoided to facilitate understanding, enabling the reader to concentrate on how the biological environment affects the performance of the drugs and dosage forms. As the majority of drugs are administered via the oral route a large proportion of the book is devoted to the gastrointestinal tract and the variation in the capacity for drug absorption which occurs along its length. Transdermal, ocular, pulmonary and nasal drug delivery are discussed in detail. New chapters in the book include 'Vaginal drug delivery', the 'Blood brain barrier' and 'Parenteral drug delivery'.

Product Details

ISBN-13:	9780748406104
Publisher:	Taylor & Francis
Publication date:	12/21/2000
Series:	Taylor & Francis Series in Pharmaceutic
Edition description:	REV
Pages:	328
Product dimensions:	7.00(w) x 10.00(h) x (d)
Age Range:	18 Years

About the Author

Neena Washington, Clive Washington and Clive G. Wilson

Table of Contents

1. Cell Membranes, Epithelial Barriers and Drug Absorption 2. Parenteral Drug Delivery 3. Drug Delivery to the Oral Cavity or Mouth 4. Oesophageal Transit 5. The Stomach 6. Drug Absorption from the Small Intestine 7. Drug Delivery to the Large Intestine and Rectum 8. Transdermal Drug Delivery 9. Nasal Drug Delivery 10. Pulmonary Drug Delivery 11. Ocular Drug Delivery 12. Vaginal and Intrauterine Drug Delivery.

Preface

Preface

Considering the variety in the human race, height, weight, temperament, enzymatic capacity, it is amazing that pharmaceuticals work at all. Add environmental factors, and personal preferences, and suddenly you begin to realise the scale of the problem. Some years ago I ran a clinical trial in patients with ulcerative colitis. When I was recruiting the subjects, I asked people to keep a diary of everything that they ate. Even within the catchment area of Queen's Medical Centre in Nottingham, the diversity of food eaten, let alone the frequency of eating, was beyond comprehension. This led me to think about the world outside Nottingham, eating habits within the UK, the north/south divide (which we are assured by the Government does not exist) let alone what people eat in Africa, China, Fiji ?? Then remember that medication is designed for sick people, who by definition have a physiology disordered in some way. So how can one pill fit all?

The development work is aimed at the "average" patient. Is there such a thing as an average patient? Is the "average" person really a 70 kg man? In the U.K. 41 % of males and 20% of females are overweight. Even the "average" healthy woman may be excluded from pharmacokinetic trials not only due to the risk of potential genetic damage to reproductive tissue but also a tacit admission that the menstrual cycle may affect not only gastrointestinal transit, but also a wide range of physiological processes. This leaves basic data concerning the behaviour of drugs in women largely undiscovered until they are treated as patients.

The realisation that the USP dissolution test bore little resemblance to dosage form behaviour in the body, particularly for the new sophisticated dose forms, led to the first edition of this book being written ten years ago. Over the past 30 years, a predominant focus of drug delivery has been the development of sustained and controlled release formulations, whose interaction with the body is even more critical and complex than that of `ordinary' tablets. In 1996 there were 35 pharmaceutical products based on advanced drug delivery with a worldwide sales of ten million US dollars each or higher; this was 11 more than in 1994. In these two years total sales had increased from 5.5 to 6.5 billion dollars. Four products were responsible for more than half of the total sales in 1996; these were ProcardiaXL (nifedipine), Lupron (leuprolide), Cardizem (diltiazem) and Zoladex (goserelin).

The primary goals are usually to minimise the dose of drug administered and to optimize the delivery of the drug, to achieve an `ideal' plasma-concentration time profile. An added advantage is that simplification of the dosage regimen leads to increased patient compliance by reducing the number of daily doses. With the new requirement to deliver drugs to precise locations of the gastrointestinal tract came the need to study physiological variations in gastrointestinal transit, such as those brought about by eating, levels of physical activity and chronobiological effects. The focus on once-a-day dosing necessitated larger payloads of drugs per unit than conventional counterparts. Premature release of the drug could have potentially disastrous effects, so prediction of dosage form behaviour needs to be accurate.

With the leap in the number of sophisticated technologies reaching the market place the amount of literature which has become available since 1990 is considerable, and hence the second edition of "Physiological Pharmaceutics" is a complete re-write and not just an update. We are very aware that people placed advance orders for this book and we would like to thank them for buying it on faith. We also would like to thank them for their patience and we hope that they feel that the wait was worthwhile. We would like to thank our publishers, who I am sure, at times, thought the manuscript was a figment of the imagination (either theirs or ours). Ironically, the first draft of the manuscript was delivered to them 3 years to the day late. By way of an explanation for the tardiness of this book, I would like you to realise that this book was written in "our spare time", as if scientists with full time jobs and a young family have "spare time"! The university obsession with the research assessment exercise has made the production of textbooks a rather low priority, so much of the volume has been written after 11 at night!

For this very reason I would like to thank our children, Alex (9 years) and Sarina (4 years) for their patience whilst mummy was writing oz daddy was drawing diagrams, and Alex for `helping' with the diagrams... We are painfully aware that it is they who have suffered as we have had virtually no time for them, particularly over the last year. As I write this, they know that the "end of book" promised trip to LegoLand is coming closer!

I also must thank my friends and colleagues, Drs Caroline Herd, Mike Nassim, Gerry Hooper and Carol Astbury for their caring and support. I would also like to thank my husband, who saw the vast amount of work which needed to be done on the book and mucked in. In acknowledgement of his substantial contribution,we made him a full author on this edition. Without him, the book would probably have been 6 years late!

Neena Washington
14, February 2000

Editorial Reviews

The authors, all specialists in pharmaceutics, provide an integrated approach to the study of drug formulations in the body, focusing on the formulation variables rather than the drugs. The book is organized by the particular mode of drug delivery, including mouth, stomach, small intestine, and large intestine, and transdermal, nasal, pulmonary, ocular, and vaginal drug delivery. Each chapter explains the anatomy and physiology of the system under discussion, specific methods of drug delivery using this system, and topics such as factors influencing drug absorption or retention, and complications. Annotation c. Book News, Inc., Portland, OR (booknews.com)

Booknews