Dermatologic,

Cosmeceutic, and

Cosmetic Development

Dermatologic,

Cosmeceutic, and

Cosmetic Development

Therapeutic and Novel Approaches

Edited by

Kenneth A. Walters

An-eX Analytical Services Ltd.

Cardiff, United Kingdom

Michael S. Roberts

School of Medicine, University of Queensland

Princess Alexandra Hospital

Buranda, Australia

Informa Healthcare USA, Inc. 52 Vanderbilt Avenue

New York, NY 10017

© 2008 by Informa Healthcare USA, Inc. Informa Healthcare is an Informa business

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International Standard Book Number-10: 0-8493-7589-4 (hb : alk. paper) International Standard Book Number-13: 978-0-8493-7589-7 (hb : alk. paper)

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Library of Congress Cataloging-in-Publication Data

Dermatologic, Cosmeceutic, and Cosmetic Development: Therapeutic and Novel Approaches / edited by Kenneth A. Walters, Michael S. Roberts.

      p. ; cm.

 Includes bibliographical references and index.

 ISBN-13: 978-0-8493-7589-7 (hb : alk. paper)

 ISBN-10: 0-8493-7589-4 (hb : alk. paper)

 1. Skin—Diseases—Chemotherapy. 2. Dermatopharmacology. 3. Cosmetics—Side effects. I. Walters, Kenneth A., 1949II. Roberts, Michael S., 1949-

 [DNLM: 1. Skin Diseases—drug therapy. 2. Administration, Cutaneous.

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Preface

Skin disorders can be both physically and psychologically traumatic for the patient. Reactions can range from the extreme discomfort of infantile eczema to the painful embarrassment of teenage acne to the midlife desire to reduce facial wrinkles and hyperpigmentation. Researchers and clinicians within the pharmaceutical and cosmetic industriesstrivetofindthosetreatmentsthatwillsuccessfullyalleviatethedistressing symptoms. Basic researchers are continually searching for causative factors, be they immunologically, genetically, or environmentally mediated. As this research con- tinues, it is safe to say that there have been many recent, significant advances in our understanding of the development and morphology of normal skin, and this has led to a more reliable ability to deliver therapeutic compounds to selected targeted areas both within the skin and systemically.

This book provides an overview of the current pharmaceutical and cosmeceutical practices in the management of both major and minor skin disorders. It is divided into eight parts. The first section is concerned with specific factors affecting efficacy of topical therapy and includes an overview of the range of skin disorders, drugs used to manage these disorders, sites where an effect is sought, and how per- cutaneous absorption is affected by age, skin site, race, and skin disease or damage.

This section also considers delivery to the systemic circulation, appendages, and nails. The second section discusses pharmaceutical therapy from the viewpoint of topical absorption and covers treatment of the major skin diseases and injuries such as wounds and burns, with particular emphasis on novel approaches.

The third section introduces the underlying principles defining cosmeceuti- cals and goes on to examine their applications, sources, and formulations. The skin absorption and use of specific cosmeceuticals are then considered, covering both cosmeceutical and cosmetic agents such as hair dyes, sunscreens, oils, hydroxyacids, moisturizers, and insect repellents. The next section includes an evaluation of the evidence base for cosmeceuticals, their appropriate use, and the safety and toxicity issues.

The final portion of the book is concerned with improving therapeutic out- comes. The various methods used to improve drug transport into and across the skin, including more accurate dosing regimens, chemical penetration enhancers, physical enhancement, and the use of microneedles and high impact powder, or biolistic, delivery.

This book has been written for scientists interested in dermatological ther- apy and those concerned with the marketing of pharmaceutical and cosmeceutical products; in addition, it will prove useful to students and those involved in research and development in the pharmaceutical and cosmetic industries.

We have been fortunate to obtain the agreement of many internationally rec- ognized experts in the field of dermal pharmaceutics and cosmeceuticals to provide coverage of their specific fields of expertise. To all of our authors we extend our sincere thanks for their unreserved efforts and time.

Kenneth A. Walters

Michael S. Roberts

iii

Contents

Preface . . . . iii

Contributors . . . . viii

Introduction

1.  Skin Structure, Pharmaceuticals, Cosmetics, and the Efficacy

of Topically Applied Agents  1

Michael S. Roberts and Kenneth A. Walters

Part I: Skin Disorders and Therapies

2.  Drugs Used for Skin Diseases  11

Neil Kitson

3.  Treatment of Dermatitis  21

Chris Anderson

4.  Evolution of Cosmeceuticals and Their Application to Skin Disorders, Including Aging and Blemishes  45

Des Fernandes

5.  Biology of Skin Pigmentation and Cosmetic Skin Color Control  61

Chong Jin Loy and Raman Govindarajan

6.  Evidence-Based Cosmeceutical Therapy  97

Maria Miteva and Joachim W. Fluhr

Part II: Specific Factors Affecting Targeting and Efficacy

7.  Skin Hydration—A Key Determinant in Topical Absorption  115

Michael S. Roberts, Joke Bouwstra, Fabrice Pirot, and Françoise Falson

8.  Epidemiology of Skin Barrier Function: Host and Environmental Factors  129

Greg G. Hillebrand and R. Randall Wickett

9.  Permeability Through Diseased and Damaged Skin  157

Daniel A. W. Bucks

10.  Targeting the Pilosebaceous Gland  169

Guang Wei Lu, Susan Ciotti, Satyanarayana Valiveti, Jeffrey E. Grice, and Sheree E. Cross

11.  Drug Penetration Enhancement Through Human Nail and Skin  189

Thomas C. K. Chan, Kenneth A. Walters, Xiaoying Hui, and Howard I. Maibach

vi Contents

Part III: Topical Pharmaceuticals, Formulations, and Indications

12.  Getting the Dose Right in Dermatological Therapy  197

Adrian F. Davis

13.  Drugs for Pain and Inflammation  215

Michael W. Whitehouse, Mantu Sarkar, and Michael S. Roberts

14.  Novel Topically Active Antimicrobial/Anti-inflammatory Compounds for Acne  243

Joseph A. Dunn, Robert A. Coburn, Richard T. Evans, Robert J. Genco, and

Kenneth A. Walters

15.  Codrugs: Potential Therapies for Dermatological Diseases  255

Tadeusz Cynkowski, Grazyna Cynkowska, and Kenneth A. Walters

16.  Topical Therapeutic Agents Used in Wound Care  267

Sheree E. Cross

17.  Established and Emerging Oral Antifungals in Dermatology  283

Gérald E. Piérard, Claudine Piérard-Franchimont, Valérie Vroome, Jorge Arrese,

Pascale Quatresooz, Marcel Borgers, and Geert Cauwenbergh

18.  Hydroxy Acids and Retinoids in Cosmetic Products  297

Robert L. Bronaugh

Part IV: Topical Cosmeceuticals, Formulations, and Indications

19.  Natural Ingredients Used in Cosmeceuticals  303

24.  Efficacy, Absorption, and Safety of Essential Oils  401

Ulrich F. Schäfer, Jürgen Schneele, Sonja Schmitt, and Jürgen Reichling

25.  Sunscreens: Efficacy, Skin Penetration, and Toxicological Aspects  419

Heather A. E. Benson

Contents vii

Part V: Safety Considerations

26.  Efficacy and Safety of Tea Tree and Other Oils  437

Christine F. Carson, Kate A. Hammer, and Jesper B. Nielsen

27.  Safety Assessments Based on Exposure, Skin Permeation and Toxicity Considerations  453

William E. Dressler and Kenneth A. Walters

Part VI: Skin Assessment

28.  Noninvasive Evaluation of Skin in the Cosmetic Industry  467

Carlos Galzote, Michael Suero, and Raman Govindarajan

29.  Application of In Vivo Scanning Microscopy for Skin Analysis in Dermatology and Cosmetology  487

Lars E. Meyer and Juergen Lademann

Part VII: Improving Therapeutic Outcomes Using Chemical Techniques

30.  Chemical Penetration Enhancement: Possibilities and Problems  497

Adrian C. Williams and Kenneth A. Walters

31.  Multicomponent Formulations of Chemical Penetration Enhancers  505

Pankaj Karande, Amit Jain, and Samir Mitragotri

Part VIII: Improving Therapeutic Outcomes Using Physical Techniques

32.  Iontophoresis  517

Narayanasamy Kanikkannan, Michael Bonner, Jagdish Singh, and Michael S. Roberts

33.  DNA Transfer in the Skin  537

Gaëlle Vandermeulen, Liévin Daugimont, and Véronique Préat

34.  Pressure Waves for Transdermal Drug Delivery  557

Apostolos G. Doukas, Sumit Paliwal, and Samir Mitragotri

35.  Microneedle Arrays as Transcutaneous Delivery Devices  577

James Birchall and Keith R. Brain

36.  Needle-Free Ballistic Delivery of Powdered Immunotherapeutics to the Skin Using Supersonic Gas Flow  591

Mark A. F. Kendall