Sterilisation and Disinfection. Pharmaceutical Monographs

272 Pages·1965·4.18 MB·English

by  T. D. Whittet, W. B. Hugo, G. R. Wilkinson and J. B. Stenlake (Auth.)

PHARMACEUTICAL MONOGRAPHS
GENERAL EDITOR
J. B. STENLAKE,
D.SC,Ph.D.,F.P.S.,F.RJ.C.,F.R.S.E.
Professor of Pharmacy, University of Strathclyde
Volume 3
STERILISATION AND DISINFECTION
STERILISATION AND
DISINFECTION
BY
T. D. WHITTET B.Sc, Ph.D., F.P.S., F.R.I.C, D.B.A.
Sometime Group Chief Pharmacist, University College Hospital, London
W. B. HUGO B.Pharm., Ph.D.(London), F.P.S.
Reader in Pharmaceutics, University of Nottingham
G. R. WILKINSON
F.P.S.
WILLIAM HEINEMANN MEDICAL BOOKS LTD
LONDON
First published 1965
© T. D. Whittett, W. B. Hugo
and G. R. Wilkinson 1965
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Printed in Great Britain by
Butler & Tanner Ltd, Frome and London
GENERAL PREFACE
The aim of this series of pharmaceutical monographs is to provide
an up-to-date series of short publications for teaching general and
specialised topics to undergraduate students of pharmacy and
allied subjects. Each monograph in the series is the work of an
expert or group of experts actively engaged in teaching or practice.
For convenience, however, groups of two or more monographs on
related subjects have been collected together for publication.
Each monograph is intended to serve as the basis for a group of
lectures or tutorials in the honours and pre-honours years of
undergraduate courses in pharmacy and allied subjects in British
and Commonwealth Universities and, of necessity, some mono-
graphs are slanted towards the more specific requirements of these
countries. We have, however, endeavoured to keep the mono-
graphs on a general plane to ensure their suitability for use in other
parts of the world.
An attempt has been made to present the subject matter of in-
dividual monographs in such detail that it provides a permanent
record for study purposes capable of being used by students in lieu
of lecture notes. Each monograph, however, sets out to provide not
merely a detailed account of essential subject matter, such as would
be required for examination purposes, but also seeks to indicate its
relevance and importance to pharmaceutical studies in general. In
this respect, monographs extend naturally to the boundaries of
knowledge in all major aspects, and wherever possible present
appropriate rival views and hypotheses in sufficient detail for the
student to grasp their essential detail without reference to the
original. The texts are, however, referenced to provide additional
sources of information.
I am indebted to the authors of the individual monographs for
their willingness to collaborate with me in the preparation of this
series. I should also like to express my thanks to my colleagues and
many friends for their help and advice in framing the series and for
discussions on individual monographs. I should further like to
express my sincere thanks to Mrs S. Cohen for invaluable secre-
tarial assistance.
J. B. S.
ν
PREFACE TO VOLUME 3
The present volume may be regarded as a sequel to the Introduction
to Microbiology published in Volume 1 of this series. The prepara-
tion of sterile pharmaceutical products requires the adoption of
techniques aimed at the complete elimination of contamination
by micro-organisms, whether they be pathogenic or not. Some
knowledge of microbiology is, therefore, essential for a proper
understanding of the methods employed, and a level of knowledge
equivalent to that reached in Volume 1 of this series is, therefore,
assumed. The monograph on sterile products surveys the types of
preparations required to be produced in a sterile condition and
considers in detail the methods available for sterilisation. It
includes discussion of some of the many problems which arise
when the various procedures are adopted in practice.
All injections must comply with the official tests for sterility.
The general methods of sterility testing and the special problems
which arise in the application of sterility tests to such specialised
products as oily injections, antibiotics and surgical dressings are,
therefore, dealt with in detail and form the subject of a separate
monograph.
In recent years, considerable attention has been focused on the
efficiency of autoclaves, whether they be small-scale units for the
extemporaneous preparation of injections or on a much larger
scale for industrial or hospital use. Some knowledge of the
principles of autoclave design, of possible design faults, or of the
advantages and disadvantages of various types of autoclave is
important not only to the user, but also to those who have respon-
sibility for the purchase and maintenance of autoclaves. The short
monograph on autoclave design which forms part of this volume
is intended to fill this need.
The problems of disinfection, whether this be of skin, or of
working surfaces, floors or drains in a laboratory, hospital or
factory, all rest fundamentally on a knowledge of the conditions
which must be generated to ensure a virtually 100% kill of
infecting micro-organisms. A knowledge of the types of dis-
infectant available, mode of action so far as it is known, factors
affecting activity, advantages and limitations, is essential for a
proper understanding of the value and use of disinfectants. The
vi
PREFACE
present monograph is intended to provide a firm foundation for
the proper use of disinfectants in practice, which can also serve as
the basis for further study on the part of those who may be called
upon to exercise this knowledge to overcome the problems of
disinfectant formulation.
One of us (W.B.H.) would like to acknowledge the helpful criti-
cism and suggestions of Professor A. M. Cook, B.Pharm., Ph.D.,
Dip.Bact., F.R.I.C., during the preparation of the monographs on
Sterility Tests and Disinfection.
Acknowledgement is also made (T.D.W.) to T. E. French,
B.Pharm., M.P.S., and I. Critchley, M.P.S., for their help in read-
ing the manuscript and for many useful criticisms and suggest-
ions, to R. Maxwell Savage, M.A., Ph.D., for his help with the
section on autoclaves and to P. R. Hills, M.Sc, Ph.D., F.R.I.C.,
for assistance with the subject of radiation and sterilisation.
T.D.W.
W.B.H.
G.R.W.
vii
CHAPTER 1
INTRODUCTION
DEVELOPMENT OF PARENTERAL THERAPY
Sir Christopher Wren, in 1656,1 assisted by the Hon. Robert
Boyle and Dr Wilkins, appears to have been the first person to
attempt intravenous injections into animals. Using a hollow quill,
one end of which was inserted into the vein of a dog, they injected
various substances, including alcohol and opium solution, and
succeeded in making one animal extremely drunk and producing
profound narcosis in another.2
Elsholtz3 made the first successful intravenous injection in man
and published a book on the subject entitled Clysmatica Nova in
1665. The first authenticated records of successful transfusion of
blood are those of Lower (1665-7) and Coga (1667). Transfusion
experiments are also mentioned in The Diary of Samuel Pepys on
November 14th, 1666.
Howard-Jones4 discussing the development of hypodermic
medication concluded that Lafargue was the first to employ it
systematically, beginning in 1836 with the 'inoculation' of solid
drugs as a paste. Later, in 1861, he used subcutaneous implanta-
tion of pellets, a technique which was revived in 1937 by Deansby
and Parkes for steroid and related hormones.
Rynd, in 1884, practised the hypoderrnic administration of a
solution of morphine, with the intention of exerting a local action
on the peripheral nerves. Rynd did not use a syringe, his procedure
being hypodermic infusion. The technique of hypodermic injec-
tion was devised by Wood in 1853, and in 1855 it was introduced as
a therapeutic procedure. His intention was to secure a local
analgesic action on peripheral nerves, and, although he clearly
recognised the occurrence of systemic effects, he failed to appreciate
their significance. Wood devised a syringe for giving his injections.
Hunter, in 1858, adopted Wood's technique of local injection.
The occurrence of infection at the site of injection in his first two
patients, however, led him, in 1859, to try remote injections.
These he found to be as effective as local injection and correctly
argued that the subcutaneous route was effective by reason of
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STERILISATION AND DISINFECTION
systemic absorption. Hunter introduced the word hypodermic to
distinguish his use of subcutaneous injection as a mode of systemic
administration from Wood's use of the same technique for its
supposed local action.
The ampoule, which provided a safe method for storing injec-
tion solutions, was invented by the French pharmacist, Limousin,
in 1886.
Local anaesthesia was introduced by Carl Koller in 1884, using
Cocaine, but it was not until the introduction of less toxic synthetic
anaesthetics, early in this century, that the method became widely
used. Spinal anaesthesia was tried on a dog by Corning in 1885 and
first used clinically with success by Bier in 1898. Epidural anaes-
thesia was introduced in 1901 by Sicard and Cathelin but was
popularised by Pages in 1921. Because of several tragedies with
spinal anaesthesia, it is now being replaced by the epidural method,
which is regarded as safer, especially since the introduction of
Lignocaine, a local anaesthetic that is very effective by that route.
DEVELOPMENT OF STERILISATION METHODS
The first injection to become official in the British Pharma-
copoeia was Injectio Morphinae Hypodermica, added in 1874 to
the 1867 Edition. It was retained in the 1885 Edition, and Injections
of Apomorphine and Ergotin were added. These injections were
not required to be sterilised but that of Ergotin was made up with
Camphor Water, presumably as a preservative.
The same three injections, with the addition of Injection of
Cocaine, were included in the British Pharmacopoeia of 1898.
This time they were made with boiled and cooled distilled water
and 0-5% of salicylic acid was added to the Cocaine Injection and
1-5% of phenol to that of Ergotin.
The University College Hospital Pharmacopoeia of 1907 con-
tained four solutions for injection (the title injection was then used
for preparations to be introduced into body cavities). These were
solutions of Eucaine, Glucose, Glucose and Sodium Chloride, and
Normal Sahne. They were boiled for at least 5 minutes in a flask
plugged with cotton wool; after cooling, the volume was adjusted
with boiled water.
The British Pharmacopoeia 1914, however, still gave no instruc-
tion for the sterilisation of medicaments, the injections being pre-
pared with recently boiled and cooled distilled water, and it was
6
INTRODUCTION
not until the 1932 Edition that sterilised injections became official.
The methods then introduced from current bacteriological prac-
tice were Autoclaving, Tyndallisation, Filtration and the Emer-
gency Method.
Tyndallisation was soon shown by Davis6 to be unsatisfactory
for many pharmaceutical products. This method consists of heat-
ing the solution at 80°* for one hour on three successive days.
Theoretically vegetative forms are killed by the first heating, and
spores should germinate the vegetative form and be killed by the
subsequent heatings. This sequence readily occurs in culture media
but Davis showed that many medicaments prevent spore germi-
nation and consequently are not sterilised by the method. The
First Addendum (1936) to the 1932 British Pharmacopoeia decreed
that aseptic technique should be used with Tyndallisation and this
largely removed its usefulness.
The Emergency Method consisted of preparing the solution by
aseptic methods and heating with an antiseptic as effective as
0-5% of phenol for 30 minutes at 80° or, for intravenous injections,
boiling for 30 minutes without an antiseptic. Both Tyndallisation
and the Emergency Method were replaced by the method of
'Heating with a Bactericide' which resulted from the work of
Berry,7 Coulthard8»9 and Davis.10»11
Other pharmacopoeias introduced sterilisation methods at about
the same time. Davis5 and Berry12 summarised the methods in use
in the pharmacopoeias of various countries between 1926 and
1935. Autoclaving was official in those of the United States, Bel-
gium, Switzerland, Italy, Germany, Denmark and Holland, whilst
those of Spain, Switzerland, Italy, Germany, Denmark, Portugal
and Hungary allowed boiling or steaming for from 15 to 60
minutes. Intermittent heating with different times, temperatures
and numbers of heatings, was official in the pharmacopoeias of
the United States, Switzerland, Italy, Germany, Holland, Spain,
France, Portugal and Hungary. The Portuguese Pharmacopoeia
directed the use of aseptic precautions with Tyndallisation, the
Hungarian gave a range of temperatures for storage during
intervals between heating, and that of the United States allowed
the method only for solutions in which bacteria can multiply.
Most pharmacopoeias included Filtration, and a few, preparation
by aseptic methods.
* All temperatures in this monograph are in ° C except where otherwise
stated.
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STERILISATION AND DISINFECTION
The International Pharmacopoeia in volume Π, published in
1955, adopted Autoclaving, Heating with a Bactericide, Filtration
and Dry Heat.
The British Pharmacopoeia of 1963 has recognised sterilisation
with ethylene oxide and ionising radiations for certain powdered
substances. This latter method may also be useful for plastics and
rubber articles.
PREPARATIONS REQUIRING STERILISATION
The purpose of sterilising pharmaceutical preparations is to
prevent the infection of body tissues, cavities or fluids with
organisms that may produce disease or damage. Contamination
may arise from non-sterile vessels or drugs, from the hands, nose
or mouth of the operator or from the air. Initial contamination
may be minimised by strict cleanliness, by special techniques and
by setting aside a specially prepared suitably organised and equipped
room or department for the preparation of sterile products.
The following types of preparation are almost always supplied
sterile:
parenteral injections,
solutions for radiographic examination of the genito-urinary tract,
solutions for bladder investigations,
solutions for peritoneal dialysis,
preparations to be applied to wounds, extensive burns or to be
introduced into certain body cavities,
preparations for use during surgical operations,
certain preparations for oral use,
implants,
eye drops and ointments,
lubricants for instruments such as catheters and speculae,
surgical dressings,
ligatures and sutures.
PARENTERAL PREPARATIONS
The term parenteral therapy literally means the administration
of drugs by any route other than the alimentary tract, but is now
generally restricted to injection methods. Solutions for irrigation
of the bladder or vagina were formerly called injections but are
now known as irrigations.
8