Topics in Topicals: Current Trends in the Formulation of Topical Agents

126 Pages·1985·2.08 MB·English

by  Professor Ronald Marks (auth.)

TOPICS IN TOPICALS
TOPICS IN
TOPICALS
Current Trends in the Formulation of
Topical Agents
Edited by
R. Marks
Department of Medicine
University of Wales College of Medicine
Cardiff
~ MTP PRESS LIMITED
~~
a member of the KLUWER ACADEMIC PUBLISHERS GROUP
- LANCASTER / BOSTON / THE HAGUE / DORDRECHT
Published in the UK and Europe by
MTP Press Limited
Falcon House
Lancaster, England
British Library Cataloguing in Publication Data
Topics in topicals: current trends in the
formulation of topical agents.
1. Skin-Diseases-Chemotherapy
2. Dermatopharmacology
I. Marks, R.
615'.778 RL110
Published in the USA by
MTP Press
A division of Kluwer Boston Inc
190 Old Derby Street
Hingham, MA 02043, USA
Library of Congress Cataloging in Publication Data
Main entry under title:
Topics in topicals.
Includes bibliographies and index.
1. Dermatopharmacology. 2. Drugs-Dosage forms.
I. Marks, Ronald.
RL80l.T67 1984 615' .778 84-23404
ISBN-13: 978-94-010-8673-8 e-ISBN-13: 978-94-009-4906-5
DOl: 10.1007/978-94-009-4906-5
Copyright © 1985 MTP Press Limited
Softcover reprint of the hardcover I st edition 1985
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,
without prior permission from the publishers.
Typesetting by Georgia Origination, Liverpool
Contents
List of Contributors 7
Introduction 9
1. Acne caused and treated by topical agents 11
W. J. Cunliffe
2. Unwanted side-effects from topical agents and tests for them 23
R. Marks
3. Psychorheology of topical applications 41
M. I. Barnett
4. What do you do with a topical corticosteroid? 47
R. Marks
5. Microbial contamination of creams 61
J.R. Morgan
6. Conquering the skin barrier 69
B. W. Barry
7. Release of drugs from topical preparations and their
subsequent fate 77
J. Hadgraft
8. The clinical relevance of in vitro investigations for
percutaneous absorption 91
B. W. Barry
9. The permeability of abnormal skin 103
R. C. Scott
10. Topical and oral preparations of glyceryl trinitrate -
A comparative study 113
M. J. Lewis, A. Bashir and A. H. Henderson
11. The influence of formulation on percutaneous absorption 121
I. W. Kellaway
12. Pharmacological and physical measurement of drug
penetration into the skin 127
M. I. Foreman
Index 133
List of Contributors
Dr M. I. Barnett Dr J. Hadgraft
The Welsh School of Pharmacy Department of Pharmacy
University of Wales Institute of The University of Nottingham
Science and Technology University Park
King Edward VII Avenue Nottingham
Cardiff NG72RD
CFl3NU
Professor B. W. Barry Professor A. H. Henderson
Postgraduate School of Studies in Department of Cardiology
Pharmacy University of Wales College of
University of Bradford Medicine
Bradford, W. Yorks Heath Park
BD7 lOP Cardiff
CF44XN
Dr A. Bashir
Department of Cardiology
University of Wales College of Professor I. W. Kellaway
Medicine The Welsh School of Pharmacy
Heath Park University of Wales Institute of
Cardiff Science and Technology
CF44XN King Edward VII Avenue
Cardiff
Dr W. J. Cunliffe CFl3NU
The General Infirmary at Leeds
Great George Street
Leeds Dr M.J. Lewis
LSI3EX Departments of Pharmacology and
Therapeutics
Dr M. I. Foreman University of Wales College of
Organon Laboratories Ltd Medicine
Newhouse Heath Park,
Lanarkshire Cardiff
MLI5SH CF44XN
7
8 TOPICS IN TOPICALS
Professor R. Marks Dr R. C. Scott
Department of Medicine Central Toxicology Laboratory
University of Wales College of Imperial Chemical Industries PLC
Medicine Alderley Park
Heath Park NT. Macclesfield
Cardiff Cheshire
CF44XN SKIO 4TJ
Dr J. R. Morgan
Department of Bacteriology
University of Wales College of
Medicine
Heath Park
Cardiff
CF44XN
Introduction
Substances that are applied to the skin to heal it, make it feel better or
improve its appearance, have much in common. They can all do
damage to the skin as well as perform the task for which they were
designed. They and the substances they contain are all absorbed
through the skin to a greater or lesser extent. In addition, all these
agents are constructed in the same general way. For these reasons it
seems odd and uneconomical to consider topical pharmaceuticals,
toiletry products and cosmetics separately. This was the reasoning
behind the holding of a small symposium of workers involved with
one or another aspect of the formulation of substances destined for
application to the skin. Several aspects of the subject are covered in
this book which is based on the symposium and the contents should
be of interest to all who are concerned with the prescription, assess
ment or formulation of topical agents.
9
1
Acne Caused and Treated
by Topical Agents
W. J. CUNLIFFE
The four main aetiological factors involved in the development of
acne are (1) an elevated sebum excretion ratel; (2) ductal hyper
keratinization 2; (3) an abnormality of microbial function3; (4) host
inflammatory response4• Although opinions differ on both sides of
the Atlantic, most authorities in the United Kingdom believe that
increased sebum excretion rate is the main drive to acne, there being a
definitive relationship between the severity of the acne and the
seborrhoea of this disease.
The aim of this paper is to discuss factors which induce or treat
acne by topical application.
TOPICAL INDUCTION OF ACNE
In this section the topical induction of acne by substances which affect
sebum excretion, ductal micro flora, mediators of inflammation and
ductal hyperkeratinization will be considered.
Topical induction by altering sebum production
Androgens are the major causative factor in acne 5 • The topical
application of androgens to one side of the forehead will increase the
sebum excretion on that side. Androgens are absorbed and if applied
in large enough amounts will increase sebum excretion at other sites.
However, this effect is seen only in prepubertal subjects, and to some
11
12 TOPICS IN TOPICALS
extent in adult females, and has virtually no effect in adult males since
their sebaceous glands are maximally stimulated. Whether or not the
topical application of androgens will actually precipitate acne has not
been proven clinically, as topical therapy with androgens is not
commonly used in the treatment of skin diseases. Nevertheless it is
theoretically possible that the long-term application of topical
androgens in prepubertal subjects and in females with a low sebum
excretion would induce acne.
Topical induction by altering the microflora
Experimental evidence shows that polythene occlusion to the skin
increases the number of the normal bacterial flora at that site, and a
whole range of inflammatory lesions can be produced by polythene
occlusion if a pathogenic strain is placed beneath it 6. We know that
acne may be induced under conditions of high humidity but there are
no laboratory data to help us decide whether or not this induction is
due to a change in the microftora. There is evidence to suggest that
changes in the microenvironment, and consequently in the
micro flora, influence the development of acne vulgaris The topical
7.
application of corticosteroids will also induce acne. The mechanism,
however, is uncertain. It may cause hyperkeratinization of the pilo
sebaceous duct Recent studies using betamethasone valerate as the
8.
corticosteroid of choice failed to demonstrate an increase in the
number of Propionibacterium acnes, which is probably the most
important organism involved in acne 9•
Topical induction by mediators of inflammation
It is unlikely that the acne vulgaris will be precipitated by the topical
application of substances inducing inflammation, but a pseudo-acne
situation can occur as a result of the primary irritant dermatitis seen
with many of the more effective topical therapies such as vitamin A
acid and benzoyl peroxide 10. This is particularly so early in treatment,
and this apparent flare in the acne must be discussed with the patients,
otherwise they will stop the treatment prematurely.