Full download ebook at ebookgate.

com

Suppositories 1st Edition Loyd V. Allen

https://ebookgate.com/product/suppositories-1st-
edition-loyd-v-allen/

Download more ebook from https://ebookgate.com

More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Check Point NG VPN 1 Firewall 1 Advanced Configuration

and Troubleshooting 1st Edition Allen V. Keele

https://ebookgate.com/product/check-point-ng-
vpn-1-firewall-1-advanced-configuration-and-troubleshooting-1st-
edition-allen-v-keele/

Instructor s Manual to Physics Laboratory Manual 4th

Edition David Loyd

https://ebookgate.com/product/instructor-s-manual-to-physics-
laboratory-manual-4th-edition-david-loyd/

A companion to Woody Allen Allen

https://ebookgate.com/product/a-companion-to-woody-allen-allen/

Michael Allen s 2008 E learning Annual 1st Edition

Michael W. Allen

https://ebookgate.com/product/michael-allen-s-2008-e-learning-
annual-1st-edition-michael-w-allen/
Internet security and firewalls 1st Edition V. V.
Preetham

https://ebookgate.com/product/internet-security-and-
firewalls-1st-edition-v-v-preetham/

Dead Ringer Allen Wyler

https://ebookgate.com/product/dead-ringer-allen-wyler/

Volume V Nicholas V. Riasanovsky (Editor)

https://ebookgate.com/product/volume-v-nicholas-v-riasanovsky-
editor/

Think Stats 1st Edition Allen B. Downey

https://ebookgate.com/product/think-stats-1st-edition-allen-b-
downey/

Living With Stress 1st Edition Allen R.

https://ebookgate.com/product/living-with-stress-1st-edition-
allen-r/
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

Suppositories

i
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

ii
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

Suppositories

Loyd V Allen, Jr
PhD
Professor Emeritus
College of Pharmacy
Health Sciences Center
The University of Oklahoma, USA
and
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Edmond, OK, USA

with contributions by

Dennis B Worthen
PhD
Lloyd Scholar
Lloyd Library and Museum
Cincinnati, OH, USA
and
Adjunct Professor
College of Pharmacy
University of Cincinnati
Cincinnati, OH, USA

and

Bill Mink
BSc
Technical Services Engineering Manager
Paddock Laboratories, Inc.
Minneapolis, MN, USA

London • Chicago

iii
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

Published by the Pharmaceutical Press

An imprint of RPS Publishing

1 Lambeth High Street, London SE1 7JN, UK

100 South Atkinson Road, Suite 200, Grayslake, IL 60030–7820, USA


c Pharmaceutical Press 2008

is a trade mark of RPS Publishing

RPS Publishing is the publishing organisation of the Royal Pharmaceutical

Society of Great Britain

First published 2008

Typeset by Aptara, New Delhi, India

Printed in Great Britain by Cromwell Press, Trowbridge, Wiltshire

ISBN 978 0 85369 646 9

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, without the
prior written permission of the copyright holder.
The publisher makes no representation, express or implied, with regard to
the accuracy of the information contained in this book and cannot accept
any legal responsibility or liability for any errors or omissions that may be
made.
The right of Loyd V Allen, Jr, to be identified as the author of this work
has been asserted by him in accordance with the Copyright, Designs and
Patents Act, 1988

A catalogue record for this book is available from the British Library

iv
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

Contents

Preface ix
About the author x

1 Introduction to suppositories 1

What is a suppository? 2
Uses and applications 3
Advantages of suppositories 4
Disadvantages of suppositories 4
Background 5
Synonyms/definitions/descriptions 6
Extemporaneous compounding 11
References 11

2 History and development of the suppository 13

Dennis B Worthen

Definitions: Suppository, pessary, bougie 13

Early history 13
Modern period 15
Suppository molds 16
Official status 19
Commercial manufacturing 19
Summary 24
References 24

3 Suppository bases and their characteristics 27

Classification of suppository bases 27

Development of suppository bases 46
References 48

v
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

vi Contents

4 Pharmaceutic, biopharmaceutic, and pharmacokinetic factors involving

suppositories 51

Anatomical and physiological considerations 51

Bioavailability of rectal suppositories 54
Physicochemical factors 54
Bioequivalence 57
Contemporary studies on the bioavailability of suppositories 58
Miscellaneous 69
References 69

5 Formulation considerations 77

Drug selection 78
Base selection 78
Formulation variables 80
Formulation studies of suppositories in the literature 81
Absorption enhancers 86
References 93

6 Manufacturing suppositories 99
Bill Mink and Loyd V Allen, Jr

Melt-fusion method 99
Cold compression method 102
General controls relative to manufacturing all suppositories 102

7 Compounding suppositories 105

Physicochemical considerations 105

Bases 107
Preparation 108
Preparation by compression 116
Special problems 117
Summary 119
References 119

8 Special types of suppositories 121

Non-rectal suppositories – vaginal suppositories 121

Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

Contents vii

Non-rectal suppositories – urethral suppositories 123

Controlled-release suppositories 123
Coated microsphere/microcapsule suppositories 123
Emulsion and emulsion–gel suppositories 124
Hollow-type suppositories 124
Hydrogel suppositories 126
Layered double or triple suppositories 127
Matrix–agar suppositories 128
Matrix–wax suppositories 128
Mucoadhesive suppositories 128
Nanoparticle suppositories 129
Osmotic suppositories 129
Prolonged-release suppositories 129
Sectile or bisected suppositories 129
Reversed micellar solution suppositories 130
Sustained-release suppositories 130
Thermo-reversible-liquid suppositories 132
Xerogel suppositories 133
Miscellaneous suppositories and bases 133
References 134

9 Quality control of suppositories 139

Physical analysis 139

Chemical testing 147
Content uniformity testing 152
Conductivity 153
Chemical testing procedures 153
Aging and aging tests 156
References 156

10 Packaging and labeling of suppositories 159

Packaging 159
Labeling 165
References 165

11 Stability and storage of suppositories 167

Physical stability 167

Chemical stability 168
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

viii Contents

Factors affecting stability 168

Microbiological stability 169
Stability studies for suppositories 169
Beyond-use dating for compounded suppositories 170
Expiry dating for manufactured suppositories 170
Storage of suppositories 170
Holding and distribution 171
Transportation 171
Responsibility of pharmacists 171
Drug-specific stability studies 173
References 175

12 Clinical considerations 177

Clinical response factors 177

Patient counseling 177
General toxicity 178
Local toxicity 179
Adverse reactions to suppositories 179
Contemporary studies of clinical effectiveness 180
References 198

Appendix I Glossary 213

Appendix II Compounding formulas 215
Appendix III Manufacturing formulas 225
Appendix IV Calculations involving suppositories 231
Index 235
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

Preface

A COMPREHENSIVE volume on the suppository and status of the suppository at the turn of the
has not been compiled in about 50 years. It twenty-first century.
was a daunting task to assimilate, evaluate, and Appreciation is extended to all those scientists
organize the material that spans several thousand over the years who have spent time in the
years of history and then emphasize the last research laboratories and to those clinicians who
25 years to compile this book on one of very have worked with patients and have provided
few dosage forms that can be traced throughout much of the background of information pulled
history. The topic is also interesting because it together for this book.
encompasses so many different aspects of phar- Appreciation is also extended to Dr Dennis
maceutics, biopharmaceutics, and pharmaco- Worthen, Lloyd Scholar of the Lloyd Library in
kinetics. Cincinnati, Ohio, for his chapter on the history
The literature review in this volume is gener- and development of the suppository, and to Bill
ally limited to the past 25 years. It was felt this Mink of Paddock Laboratories in Minneapolis,
was necessary because to some degree, what is Minnesota, for contributing to the chapter on
published often tends to repeat itself. Therapeutic manufacturing suppositories.
and scientific advances tend to be reinforced so
it was decided to simply glean from over 2500 Loyd V Allen, Jr
references those we felt best illustrated the story July 2007

ix
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:2

About the author

Loyd V Allen, Jr is Editor-in-Chief of the velopment to the pharmaceutical industry both

International Journal of Pharmaceutical Compound- nationally and internationally.
ing, CEO of the Midwest Institute of Research Loyd V Allen, Jr has received numerous awards
and Technology, and Professor Emeritus of the and has served on many US Pharmacopeia Com-
University of Oklahoma College of Pharmacy, mittees continuously since 1980. He has super-
Oklahoma, USA. vised 25 MS and PhD students and was awarded
He taught at the University of Oklahoma 13 patents in drug formulations. He has pub-
College of Pharmacy for almost 30 years where he lished over 200 experimental publications and
was Professor and Chair, Department of Medici- abstracts, 25 books, chapters and monographs,
nal Chemistry and Pharmaceutics. In 1996, he over 400 professional publications, 21 film/book
founded the International Journal of Pharmaceu- reviews, and has authored or co-authored four
tical Compounding, now circulated to over 80 textbooks.
countries. He is a consultant in formulation de-

x
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

1
Introduction to suppositories

OFTEN SEEN AS a neglected dosage form, suppos- postmenopausal women. The use of HRT with
itories have not gained the level of acceptability, “bio-identical hormones,” which are identical
respect, and usage of most other methods of to the hormones produced by the body rather
administering medications. Nevertheless, a con- than synthetic or semi-synthetic hormones, is
siderable amount of work on suppositories has becoming increasingly popular in the treatment
been conducted in recent years as evidenced by of postmenopausal symptoms (flushing, night
a literature search on the terms “suppository” or sweats, mood swings, etc.).3
“suppositories.” In the past 50 years, there have Even though they have never been very pop-
been over 4000 citations on MEDLINE,1 with ular as a mode of administering drugs, sup-
most of the work having been done in Europe positories will probably always have a place in
and in the United States. medicine. They are primarily employed for three
Suppositories are solid dosage forms intended reasons:
for insertion into body orifices (rectum, vagina
1 to promote defecation,
or urethra), where they melt, soften, or dissolve
2 to introduce drugs into the body, and
and exert localized or systemic effects. The word
3 to treat anorectal diseases.
“suppository” is from the Latin supponere, mean-
ing “to place under,” derived from sub (under) Psychologically, suppositories possess consider-
and ponere (to place). Thus, suppositories are able placebo effect in the treatment of anorec-
described both linguistically and therapeutically tal disorders. The user feels that something is
to be placed “under” the body, as into the really being done at the site involved and this
rectum. The use of rectal suppositories has been results in a positive attitude towards the mode
documented for many centuries, and far back as of treatment of the disease or disorder. This may
the Ancient Egyptian civilization. promote hope and the possibility of avoiding the
In general today, suppositories are used more embarrassment of telling family and friends what
routinely in southern European countries and is happening in the private area.
in Latin American countries than in northern Regardless of the remedy employed, some
European and Anglo-Saxon countries. In the anorectal disorders resolve without any treat-
United States, fewer than 1% of drugs are for- ment whatsoever. Nevertheless, if the symptoms
mulated as suppositories, whereas in Germany it subside after suppository usage, then clearly the
may be as high as 5%.2 suppository gets the credit.
Although there continues to be a trend away Rectal administration is not often the first
from rectal delivery for routine administration route of choice but it sometimes becomes a good
of drugs, urethral and vaginal suppositories are alternative when the oral route is inadvisable.
becoming more acceptable in some areas. For The relatively low cost and lack of technical
example, urethral suppositories are used in the difficulties make rectal drug administration at-
treatment of male erectile dysfunction (MUSE, tractive when compared with parenteral therapy.
alprostadil; Vivus Inc., California, USA) and in The downsides of rectal administration include
the past 5–10 years in the USA, progesterone esthetics and the stigma of violating the patient’s
vaginal suppositories have become more popu- dignity; these factors, along with potential rectal
lar for hormone replacement therapy (HRT) for irritation due to frequent administration, and

1
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

2 Suppositories

often it does not. Some clinicians have made their

Table 1.1 Analgesic suppositories commercially
own extemporaneous “suppositories” by putting
available in the USA morphine tablet triturates in empty gelatin cap-
sules. This extemporaneous preparation allows
Drug Strengths available (mg) easy dose titration and this method may be
more economical and as well-tolerated as the
Aspirin 60, 120, 125, 200, 300, 600
commercial suppositories.
Acetaminophen 80, 120, 125, 325, 650
Hydromorphone 3
Indometacin 50
Morphine 5, 10, 20, 30 What is a suppository?
Opium + belladonna 30 + 16.2, respectively
extract
Oxmorphone 5 The differing views of various groups should
be considered when looking at definitions of
From Anon. Physicians’ Desk Reference-PDR, 61st edn. Montvale, NJ: suppositories. They are seen very differently by
Thomson PDR, 2007.
different individuals.
To the patient, a suppository is a medication
inserted into the rectal or vaginal cavity that con-
difficulty in titrating a correct dose due to limited tains an “active” ingredient designed to cause a
strengths of commercial suppositories, pose some certain effect. More specifically, it is a small, solid
challenges. “thing” that is either bullet or cone-shaped and
In treating patients in the last days of life (e.g. which might melt if stored in a room in the house
hospice patients), rectally administered medica- or it may melt between the fingers prior to and
tions are an essential part of palliative medicine. during administration. It also is a medicine that
Properly selected drugs and suppository vehicles may be found in the medicine cabinet along with
can enhance the quality of life of these patients. cough syrups, aspirin, acetaminophen, muscle
The importance of extemporaneously com- rubs, and others. It is also a dosage form that
pounding suppositories becomes evident when can be used in children when they are vomiting
one looks at the limited number of analgesic sup- or just will not take their medication.4
positories (Table 1.1), antiemetic suppositories To the physician, a suppository provides an
(Table 1.2), and the lack of anxiolytic and an- alternate dosage form and route of administra-
ticonvulsant suppositories that are commercially tion that can be used in treating a child or adult,
available. Many clinicians have used oral tablets, either at the hospital or in the home, without
oral capsules, oral solutions, emulsions and sus- using injections when the patient cannot take
pensions, and sometimes injectable products for the medication orally. A suppository is also an
rectal administration. Sometimes this works well; excellent dosage form for elderly and hospice
patients who cannot take oral medications and
for patients for whom it is inappropriate to give
numerous injections. It is also a dosage form
Table 1.2 Antiemetic suppositories commercially that can be administered to avoid nausea and
available in the USA vomiting caused by certain medications upon
oral administration, and it is a dosage form that
Drug Strengths available (mg)
can produce a fast onset of action as compared
Chlorpromazine 25, 100 with an oral tablet or capsule.4
Prochlorperazine 2.5, 5, 15 To the pharmacist, a suppository is a dosage
Promethazine 12.5, 25, 50 form that requires consultation with the pa-
Thiethylperazine 10 tient to ensure proper storage, administration
Trimethobenzamide 100, 200 and usage. Many suppositories are commercially
available but many have to be compounded.
From Anon. Physicians’ Desk Reference-PDR, 61st edn. Montvale, NJ:
Thomson PDR, 2007.
Compounded suppositories can be prepared
using different bases for different onsets and
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

Chapter 1 • Introduction to suppositories 3

durations of action. Pharmacists generally re-

member preparing cocoa butter suppositories in Table 1.3 Official suppositories in the USP
school and often enjoy talking about the ex-
perience. Compounding pharmacists often view Acetaminophen
suppositories as a way to meet individual patient Aminophylline
needs when other routes of administration are Aspirin
not really appropriate. This is especially true for Bisacodyl
pediatric and hospice patients.4 Chlorpromazine
To the pharmaceutical manufacturer, suppos- Ergotamine tartrate and caffeine
itories are a way of presenting an active ingre- Glycerin
Indometacin
dient in a suitable dosage form. Suppositories
Miconazole nitrate vaginal
are not as widely used as capsules and tablets
Morphine sulfate
but remain an important dosage form. In many
Nystatin vaginal
cases, pharmaceutical companies outsource the
Oxymorphone HCl
manufacturing process to companies that have
Prochlorperazine
invested in newer equipment for production, Progesterone vaginal
packaging, and labeling.4 Promethazine hydrochloride
Suppositories provide many clinical benefits Triethylperazine maleate
but often go unused because of national/cultural
and patient prejudice. Some patients may have From U.S. Pharmacopeial Convention Inc., U.S. Pharmacopeia 30-National

difficulty retaining suppositories and may not Formulary 25. Rockville, MD, 2007.

always understand that the medication is not

necessarily intended to stimulate bowel activ- Previously, the rectal pathway was reserved for
ity. Another possible reason for non-use is the the administration of locally active products such
perceived lack of flexibility regarding dosage. as those used in the treatment of hemorrhoids,
Suppositories are commonly used to administer worms, and constipation. In the treatment of
systemic medication in Latin countries. In the hemorrhoids and anal fissures, the suggestion
UK, however, it has been said that the single was made at one time that the suppository should
most significant drawback of this form is the tra- be “hour glass” or “collar button” shaped so
ditional British aversion to this route. The French that it would stay in the anal canal. Many drugs
are quite content to have their temperature taken absorbed from the upper gastrointestinal tract are
via the rectum, while the British find this distaste- also absorbed in the rectum.
ful and embarrassing. The French, in general, are It is well accepted that many active ingredients
also quite content to use suppositories. Germans can be administered rectally and achieve thera-
are even more likely than the French to have no peutic blood levels. Some medications are best
problems with a rectal examination. administered by this route, and others can be if
In a large British study of phenylbutazone needed.
suppositories in general practice, 10% of the As noted earlier, suppositories contain drugs
patients refused to participate because they were such as aspirin and opiates for pain, ergotamine
not prepared to accept a suppository and half did tartrate for treating migraine headaches, and
not complete the eight-week study. Interestingly many other drugs for other uses. These drugs are
though, British physicians who commonly pre- intended to be absorbed into the general circula-
scribed suppositories found their patients more tion to provide systemic effects. Other examples
tolerant and willing to use them.5 of suppositories given for systemic results include
the following:

r Diazepam is useful as an anxiolytic for patients

Uses and applications
who cannot swallow but acts too slowly for
treating epilepsy during emergencies. Epilep-
Some examples of commonly used official sup- tic seizures in children can often be controlled
positories are listed in Table 1.3. by rectal administration of diazepam solution.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

4 Suppositories

r Metronidazole is as effective when given r It can be used to administer medication to an

rectally as intravenously. Prophylaxis with ill child who may refuse oral medication and
metronidazole suppositories has reduced the may fear injections.
incidence of postoperative anaerobic infection r It allows the administration of drugs in pa-
in patients undergoing abdominal surgery. tients experiencing nausea and vomiting or
r Progesterone is absorbed from the small intes- when the patient is unconscious.
tine but is then inactivated in the liver. Rectal r It avoids interference with drug absorption
or vaginal absorption is effective and supposi- by the presence of disease of the upper gastroin-
tories are more convenient than intramuscular testinal tract.
injection in the treatment of premenstrual r It can achieve a rapid drug effect systemically (as
syndrome. an alternative to injection).
r Aminophylline and theophylline supposito-
ries were previously used at bedtime for noc- The rectal route is often overlooked as a non-
turnal asthma and early morning wheezing, invasive method for medication administration
but the sustained-release oral preparations in patients unable or unwilling to take medica-
available today are more reliable and have tion orally. Rectal administration can be espe-
replaced them. cially useful in terminal care. In some locations,
r Morphine, oxymorphone, and oxycodone the use of suppositories may be more common in
suppositories are useful in terminal illness, the hospital; but parents and children can easily
especially when oral therapy is difficult. be shown how to insert a suppository.
r Prochlorperazine, chlorpromazine, and thi- Rectal administration can result in rapid, and
ethylperazine suppositories can help patients in many cases, extensive absorption of the active
with severe nausea or vomiting and as a ingredient. The rapidity, intensity, and duration
tranquilizer. of action are three parameters which must be
r Indometacin, diclofenac, ketoprofen, and considered during formulation for rectal admin-
naproxen can be given in suppositories; they istration and, in many cases, can be altered to
all appear to be similarly effective. meet the needs of the individual patient.
r Ondansetron suppositories are useful for the
relief of nausea and vomiting.

Disadvantages of suppositories
Advantages of suppositories
Reasons given for the infrequent use of supposi-
The advantages of rectal administration include tories include the following:
the following: r A perceived lack of flexibility regarding the
r It avoids, at least partially, the first pass effect, dosage of commercially available supposito-
which may result in higher blood levels for ries, resulting in under-use and a lack of
those drugs subject to extensive first pass availability.
metabolism upon oral administration. r Cost – if suppositories are made on demand
r It improves drug stability by avoiding the they may be expensive.
breakdown of certain drugs that are suscep- r Variable effectiveness – this depends upon
tible to gastric degradation. many factors to be discussed later, including
r It allows the administration of somewhat the pathology of the anorectal lesions.
larger doses of drugs than via the oral route. r Different formulations of a drug with a narrow
r It allows drugs to be given that may have an therapeutic margin, such as aminophylline,
irritating effect on the oral or gastrointestinal cannot be interchanged without risk of
mucosa when administered orally. toxicity.
r It allows the administration of unpleasant r A “bullet-shaped” suppository may leave the
tasting or smelling drugs. This is especially anorectal site after insertion and ascend
important in children. to the recto-sigmoid and descending colon.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

Chapter 1 • Introduction to suppositories 5

Suppositories with this shape possibly should used for either local or systemic effects. Local
not be used at bedtime. applications include the treatment of hemor-
r Defecation may interrupt the absorption pro- rhoids, itching, and infections. Systemic appli-
cess of the drug, especially if the drug is cations involve a variety of drugs, including
irritating. antinauseants, antiasthmatics, analgesics, and
r The absorbing surface area of the rectum is hormones.
much smaller than that of the small intestine.
r The fluid content of the rectum is much less
than that of the small intestine; this may affect Local action
dissolution rate, etc.
r Some drugs may be degraded by the microflora Once a suppository designed to treat locally is
present in the rectum. inserted, the suppository base melts, softens, or
Most other barriers to the use of suppositories dissolves, distributing the medication it carries
concern practice issues, such as embarrassment or to the tissues of the region. Rectal suppositories
positioning of patients when administering sup- intended for localized action are most frequently
positories. If treatment is to continue at home, used to relieve constipation or pain, irritation,
conditions such as arthritis that could hamper itching, and inflammation associated with hem-
the patient’s ability to self-administer should be orrhoids or other anorectal conditions. Antihe-
considered. morrhoidal suppositories frequently contain a
Patients sometimes have problems retaining a number of components, including local anes-
suppository; they may not understand that it is thetics, vasoconstrictors, astringents, analgesics,
a medication and is not intended to stimulate soothing emollients, and protective agents. A
bowel action. popular laxative, glycerin suppositories promote
To overcome some of the disadvantages of laxation by local irritation of the mucous mem-
suppositories, clinicians should prepare patients branes, probably because of the dehydrating
before administration: effect of the glycerin. Vaginal suppositories or
inserts intended for localized effects are em-
r Ask about any pre-existing anal conditions ployed mainly as contraceptives, antiseptics in
that might interfere with administration, such feminine hygiene, and as specific agents to
as hemorrhoids or anal fissures. combat an invading pathogen. Most commonly,
r Show the patient the suppository and re- the drugs used are nonoxynol-9 for contracep-
mind them to remove any wrapping before tion, and trichomonacides to combat vagini-
insertion. tis caused by Trichomonas vaginalis, Candida
r Explain the insertion technique. (Monilia) albicans, and other microorganisms.
r Obtain the patient’s informed consent. Urethral suppositories may be used as antibac-
r Remember that suppositories may cause pa- terials and as a local anesthetic prior to urethral
tients embarrassment and anxiety; be sensitive examination.
to their concerns about privacy and allow
them to have an open and frank discussion
before going ahead. Systemic action
r Encourage the patient to retain the supposi-
tory for the correct length of time. One contemporary question that needs to be
addressed for all active drugs to be used in
suppository dosage forms for systemic effects is
Background
the bioavailability of the drug. This is important
so that dosage adjustments can be made if nec-
Suppositories can be used to administer drugs to essary. Numerous orally administered drugs have
infants and small children, to severely debilitated relatively poor bioavailability but the dosage is
patients, to those who cannot take medications adjusted so they are effective; the same situation
orally, and to those for whom the parenteral applies with rectal or vaginal administration of
route might be unsuitable. Suppositories can be suppositories. Some information is available but
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

6 Suppositories

much more needs to be generated. This is dis-

cussed further in Chapter 4, along with data from
many literature sources on the bioavailability of
drugs in different suppository bases.
Physicians and patients usually only consider
a suppository dosage form for a specific therapy
if, under given conditions, the rectal pathway
will allow for a satisfactory rate and extent of
absorption of the active ingredients.
The overall consensus on work related to
suppositories and rectal administration is that
the suppository dosage form can be relied upon
but one must consider that active ingredients
differ in their physicochemical and biochemical
properties and that the repeated administration
conditions for a suppository are not always the
same. From the administration standpoint, rectal
absorption is variable according to the position
of the patient, the age of the patient and the
properties and secretions of the rectal mucous
membrane and the digestive tract. Hence the re- Figure 1.1 Commercially available suppositories showing
liability of rectal medication can only be assured plastic strip that is packaged inside the carton. Photo
within the broad limits of the defined conditions courtesy of Paddock Laboratories, Inc., Minneapolis, MN.
of its administration. With this in mind the
physician, pharmacist, and nursing staff must
the physical dosage form for distribution and
pay attention to these conditions.
administration.
The mucous membranes of the rectum and
The active part may be used either alone
vagina permit the absorption of many soluble
or in combination with other active ingredi-
drugs, leading to systemic effects. Although the
ents. Numerous combination suppositories are
rectum is mostly used as the site for the systemic
available and provide a convenient means of
absorption of drugs, the vagina is increasingly
administering several drugs with only one dosage
used in hormone replacement therapy using
form.
progesterone.
The inactive part, or excipient, has a role to
disperse or dilute, sometimes to protect and to
allow the introduction of the active drug into
Synonyms/definitions/descriptions the patient. After administration, the role of the
suppository is to release the active principle,
either by melting as a result of body temperature
Synonyms for suppositories include anal cones,
or by dissolving in the local mucosal fluids. The
vaginal cones, pessaries, ovules, and bougies.
active ingredient is then free to produce a local
Example are shown in Figures 1.1–1.5.
effect or to move through the mucosal barriers
into the circulatory system to produce a systemic
effect.
Anatomy of a suppository
The following statement pretty well sums up
the progression of the suppository:4
The suppository dosage form generally consists
of two parts: the active or therapeutic ingredient
and the inactive part, consisting of excipients. Basically then, this Galenic form must be de-
The former is required to produce a specific formed and transformed. In the factory, in the
therapeutic effect and the latter to provide Chemist’s store and in the nurses’ fingers, it is a
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

Chapter 1 • Introduction to suppositories 7

Figure 1.2 Commercially available suppositories. Photo courtesy of Paddock Laboratories, Inc., Minneapolis, MN.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

8 Suppositories

Figure 1.3 Various sizes and shapes of rectal suppositories.

11

12

Figure 1.4 Some examples of vaginal suppositories and

tablets.
7
macroscopically homogenous product, hard and
shiny; in the rectal cavity on the contrary, it is
a product which melts, dissolves and ensures the
delivery of the medicament.

Suppositories are commonly used rectally, vagi- Figure 1.5 Some examples of urethral suppositories.
nally, and occasionally, urethrally. They come in
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

Chapter 1 • Introduction to suppositories 9

various shapes and weights. The shape and size insertion into the male or female urethra. Male
of a suppository must be such that it is capable of urethral suppositories may be 3–6 mm in dia-
being easily inserted into the intended body ori- meter and approximately 140 mm in length,
fice without causing undue distension, and once although this may vary. When cocoa butter is
inserted, it must be retained for the appropriate employed as the base, these suppositories weigh
period. Rectal suppositories are inserted with the about 4 g. Female urethral suppositories are about
fingers (with or without fingercots or gloves), half the length and weight of the male urethral
but certain vaginal suppositories, particularly the suppository, being about 50–70 mm in length
vaginal “inserts” or vaginal tablets prepared by and weighing about 2 g.
compression, may be inserted high in the vaginal r Nasal and otic suppositories used in the nose or
vault with the aid of a special insertion appliance
ear are also called “bougies,” but are not widely
(inserter).
used.
r Rectal suppositories are usually about 1–1.5
inches (2.5–4 cm) in length, cylindrical, and have Suppositories generally consist of an active drug
one or both ends tapered or rounded. Some incorporated into an inert matrix, which may be
rectal suppositories are shaped like a bullet, a either a rigid or semi-rigid base. This intimate
torpedo, or the little finger. The shape of some mixture of the drug and inert matrix must be
is designed so that peristaltic movements will formulated to be free of any interactions between
help to move the suppository higher in the the two to avoid any alteration of either the
rectum. The weight of rectal suppositories varies, active ingredient or the inert matrix. There are
depending on the density of the base and the limitations on the quantity of active ingredient
medicaments present. Adult rectal suppositories that can be used, depending upon the size and
generally weigh about 2 g when cocoa butter desired release characteristics of the suppository.
(theobroma oil) is employed as the suppository Usually, the incorporated drug consists of a solid
base. Rectal suppositories for use by infants and (powder), but it may also be a semi-solid or
children are about half the weight and size liquid (aqueous, alcohol, oils, extracts, etc.) to be
of the adult suppositories and have a more incorporated into the base. The base material may
pencil-like shape. Examples of some rectal sup- be natural, synthetic, or semi-synthetic and is
positories and their compositions are shown in selected based upon its ability to soften, melt, or
Table 1.4. dissolve upon introduction into the body cavity.
r Vaginal suppositories, also called pessaries, are Suppositories are also intended to provide
local action within the perianal area. Local anes-
usually globular, oviform, or cone-shaped and
thetic suppositories are commonly employed to
weigh about 3–5 g when cocoa butter is the
relieve pruritus ani of various causes and the
base. However, depending on the base and the
pain sometimes associated with hemorrhoids.
individual manufacturer’s product, the weights
Commercial hemorrhoidal suppositories contain
of vaginal suppositories may vary widely. Com-
a number of medicinal agents, including astrin-
pounded vaginal suppositories that use water-
gents, protectives, anesthetics, lubricants, and
soluble bases, such as polyethylene glycol (PEG),
others, intended to relieve the discomfort of the
are the preferred form, as they are miscible with
condition. Cathartic suppositories are contact-
vaginal fluids and minimize leakage. Oil or fat-
type agents that act directly on the colonic
based suppositories are immiscible with vaginal
mucosa to produce normal peristalsis. Because
fluids and tend to leak from the vaginal orifice.
the contact action is restricted to the colon, the
Some vaginal suppositories are actually com-
motility of the small intestine is not appreciably
pressed tablets and are often called inserts. Some
affected. Cathartic suppositories are more rapid-
examples of vaginal suppositories and tablets are
acting than orally administered medication. Sup-
shown in Table 1.5.
positories of bisacodyl are usually effective in
r Urethral suppositories, also called bougies, are 15 minutes to an hour, and glycerin suppositories
slender, pencil-shaped suppositories intended for usually within a few minutes following insertion.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

10 Suppositories

Table 1.4 Examples of rectal suppositories

Corresponding Active constituent

Suppository commercial product per suppository Type of effect Category and comments

Bisacodyl Dulcolax 10 mg Local Cathartic. See text for

suppositories Suppositories additional discussion.
(Ciba) Base: hydrogenated
vegetable oil
Chlorpromazine Thorazine 100 mg Systemic Antiemetic; tranquilizer. Base:
suppositories Suppositories glycerin, glyceryl
(SmithKline monopalmitate, and
Beecham) monostearate, and
hydrogenated fatty acids
of coconut and palm
kernel oils
Hydrocortisone Anuprep-HC 25 mg Local For use in pruritis ani,
suppositories Suppositories inflamed hemorrhoids, and
(Warner-Lambert) other inflammatory
conditions of the
anorectum. Base:
hydrogenated glycerides
Hydromorphone Dilaudid Suppositories 3 mg Systemic Analgesic. Base: Cocoa butter
suppositories (Knoll) with silicone dioxide
Mesalamine Canasa (Axcan 500 mg Local Anti-inflammatory. Base: Hard
suppositories Scandipharm) fat
Oxymorphone Numorphan 5 mg Systemic Analgesic. Base: Polyethylene
suppositories Suppositories glycols 1000 and 3350
(Endo)
Prochlorperazine Compazine 2.5, 5, and 25 mg Systemic Antiemetic. Base: glycerin,
suppositories Suppositories glyceryl monopalmitate
(SmithKline and monostearate, and
Beecham) hydrogenated fatty acids
of coconut and palm
kernel oils
Promethazine HCl Phenergan 12.5 and 25 mg Systemic Antihistamic, antiemetic and
suppositories Suppositories sedative actions: used to
(Wyeth-Ayerst) manage conditions of
allergic origin; for
preoperative or
postoperative sedation or
nausea and vomiting; and
for motion sickness. Base:
cocoa butter and white
wax

From Anon. American Drug Index 2007 . St. Louis, MO: Wolters Kluwer Health, 2007.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

Chapter 1 • Introduction to suppositories 11

Table 1.5 Examples of vaginal suppositories and tablets

Product/manufacturer Active constituents Category and comments

Monistat 7 Suppositories (Advanced Miconazole nitrate, 100 mg Antifungal for treatment of localized
Care Products) vulvo-vaginal candidiasis (moniliasis)
Mycelex-7 Vaginal Tablets (Bayer) Clotrimazole, 100 mg Treatment of vulvo-vaginal yeast (Candida)
infections
Semicid Vaginal Contraceptive Nonoxynol-9, 100 mg Non-systemic, reversible method of birth control
Inserts (Robins Healthcare)

From Anon. American Drug Index 2007 . St. Louis, MO: Wolters Kluwer Health, 2007.

Some commercially prepared suppositories are morphine alkaloid suppository has been intro-
available for both adult and pediatric use. duced for chronic pain.
In summary, suppositories have been used
throughout history and are increasing in use.
Although not necessarily the first choice as a
Extemporaneous compounding
dosage form, there are many occasions where
they serve a distinct purpose for patients.
It is essential that all healthcare professionals
whose patients receive extemporaneous com-
pounds recognize the criteria by which these
medications must be formulated for optimal References
patient benefit. This knowledge can improve
healthcare professionals’ ability to communi- 1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
cate effectively about the extemporaneous com- (accessed December 29, 2006).
pounds with other providers caring for the pa-
tients and with the patients themselves. It will 2. Gold M, VePuri M, Block LH. Suppository devel-
opment and production. In: Lieberman HA, Rieger
also assist physicians in prescribing and nurses
MM, Banker GS, eds. Pharmaceutical Dosage Forms:
in administration or directing patients to phar-
Disperse Systems, Vol. 2. New York: Marcel Dekker,
macists well qualified to provide this important 1996: 447–496.
service.
The suppository dosage form is being used 3. Gillson GR, Zava DT. A Perspective on HRT for
more frequently in compounded formulations. women: Picking up the pieces after the women’s
health initiave trial, Part I. Int J Pharm Compound
For example, compounded suppositories that
2003; 7: 250–256.
contain metoclopramide, haloperidol, dexa-
methasone, diphenhydramine, and benztropine 4. Guillot BR, Lombard AP, ed. Le Suppositoire. Paris:
can be administered prophylactically to control Maloine S.A., 1973: 6–7.
severe nausea and vomiting; salbutamol can be 5. McIntosh IB, Fowler PD. Phenylbutazone suppos-
administered rectally for long-term prophylactic itories: a multi-centre general practitioner study.
treatment of asthma; and a prolonged-release, Practitioner 1977; 219: 391–395.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:12

12
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

2
History and development of the
suppository
Dennis B Worthen

The suppository is a form of medicine now very on the neighboring parts, or on the system at
rarely adopted. It is intended for the administra- large (p. 381).”3 In the 1874 edition of Dunglison’s
tion of medicinal agents to the rectum (p. 515).1 Medical Lexicon, the definition was expanded,
noting that the shape of the suppository was
This was how the Father of American Pharmacy, presented in the “form of a cone or cylinder”
William Procter, Jr, in the first pharmaceutical and that some suppositories were intended for
book adapted to the American audience, sum- insertion in the uterine cavity, cervical canal,
marily dismissed the suppository in 1849. Seven and vagina, and further that there were also
years later, in the first pharmacy text written by suppositories or medicated bougies for urethral
and for American practitioners, Edward Parrish, use.4
a fellow professor at the Philadelphia College of Over time, the terms pessary and bougie have
Pharmacy, echoed the same sentiment, noting also become associated with the suppository, al-
that he had little experience with the preparation though not necessarily as synonyms. The pessary
of suppositories.2 originally referred to a device, usually made of a
This appreciation of the suppository in mid- solid substance, which was placed in the vagina
nineteenth century pharmacy was not represen- to support the uterus or reduce a vaginal hernia.
tative of its popularity in early therapeutics or The pessary could also be medicated, in which
those of today. Indeed, the transformation of a case they were referred to as suppositories. The
low-tech delivery system into the increasingly term bougie, French for “wax candle,” initially
sophisticated modern suppository is worthy of was used for dilating passages, such as the rectum,
some understanding. urethra, and esophagus in order to remove or
reduce an obstruction or stricture. Medicated
bougies often included a caustic or escharotic
Definitions: Suppository, pessary, substance.
bougie

The historical definition of suppository has been

Early history
relatively constant since the middle of the nine-
teenth century. In his 1873 Pharmaceutical Lexi-
con, HV Sweringen defined suppositoria (supposi- In his 1953 work on the history of the anal
tories) as “solid bodies intended to be introduced suppository, Paul Diepgen addressed the sup-
into the rectum, with a view either of evacuating posed origin of instinctive healing actions and
the bowels by irritating the mucous membrane their evolution to systematic therapeutics. Part
of the rectum, or of producing a specific effect of the theory of disease and healing was that

13
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

14 Suppositories

the harmful agent must be removed from While the active ingredients of the Egyptian
the body and one way to accomplish heal- pharmacopeia have passed from use for the most
ing was to evacuate, or defecate, the harmful part, the conditions requiring intervention have
element.5 not and suppositories remain among the dosage
The origin of the suppository as a dosage forms in use three and a half millennia after the
form is hidden in the dark reaches of history. writing of the Ebers Papyrus.
Perhaps the earliest record of it occurs in an The Egyptians, and other early civilized cul-
Egyptian medical papyrus dating from approxi- tures such as the Babylonians and Assyrians,
mately 1550 BC. Acquired by Georg Ebers in 1872, believed that anal therapy had systemic conse-
the papyrus presents a compilation of writings quences based on the notion that the anus was
devoted to medicine and magic and contains a the point at which the vascular system came
large number of prescriptions and their intended together. Diepgen noted the importance of the
uses. Albeit not the oldest papyrus containing anus in the Egyptian period between 3200 and
medical information, the Ebers is the longest. 2270 BC with at least two physicians who had
It lists 811 prescriptions to treat a broad array the sobriquet “Pastor of the Pharaoh’s Anus”
of diseases as well as to provide cosmetic sug- (p. 5).5 On the other hand, ancient Indian prac-
gestions and household management hints. In tices considered suppositories to be secondary to
addition a number of dosage forms are suggested, enemas; suppository use in systemic therapeutics
including ointments, inhalations, pills, and is less clear. The suppository was especially useful
suppositories. for small children, the weak, and women, who
Purgatives for the treatment of constipation were viewed as being little more than children,
were well represented in the papyrus.1 One recipe at least in terms of therapeutics.
for a suppository, for example, included the Early Hippocratic followers used the supposi-
following ingredients (p. 45):6 tory mostly for local action, such as hemorrhoids.
r Honey
Diepgen was not able to document the belief
r Sasa-seeds
in systemic effectiveness for the dosage form.
r Wormwood
The descriptions used for suppositories referred
r Elderberry
to size, such as thick, and ingredients such as
r Berries-of-the-uan tree
hemlock and myrrh.
r Kernel-of-the-ut’ait-fruit
The concept of the whole-body effect of sup-
r Caraway
positories returned in the work of Dioscorides
r Aaam-seeds
in the first century of the Christian era. Sup-
r Xam-seeds
positories were used to restore the balance of
r Sea-salt.
humors. Diepgen notes, however, that distin-
guishing whether the suppository was for anal
Suppositories were also recommended to cool or vaginal use or insertion into a fistula was
and remove the smarting of the anus when frequently unclear. Galen, a hundred years later,
internal remedies were not effective. For exam- restricted the use of suppositories for bowel
ple, readers were instructed to take “Fat-of-the- cleansing and introduced the use of Gallic soap
Antilope” and “Caraway” and to “Roll into a (p. 9).5
Pill and put in the Anus” or to take “Cow- The suppositories of the early period, as noted
horn, Pieces-of-dried-Oil and Yeast-of-Wine” and in the Ebers papyrus, were made up of veg-
to “Make a peg (suppository) for the Man or etable, animal, and mineral ingredients that were
Woman” (p. 57).6 formed into an appropriate shape and inserted
Recommendations for women’s conditions, into the appointed orifice. Diepgen noted that
ranging from abortion, to birth, to lactation, were during the Greco-Roman period the suppository
also included. There were several suggestions to base was likely to be a fabric or lint, twisted to-
induce labor, including a vaginal suppository gether and impregnated with the medicaments.
containing “Fennel, Incense, Garlic, sert-juice, By the late Byzantine period the suppository was
Fresh Salt and Wasp’s dung” (p. 84).6 falling into disuse once again (p. 11).5
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

Chapter 2 • History and development of the suppository 15

The suppository also appears to have only it is reasonable to look at the time of significant
limited use in the period of Arabic medicine. change as an indication. By the mid-nineteenth
In the tenth century Ali Ibn Al-Abbas-al-Majusi century changes in education, regulation, pro-
mentions the suppository in his Liber Regius but fessional literature, manufacturing, and science
provides only limited use for it. In the eleventh were evident, certainly in America. The first
century, Avicenna’s fifth book of his Cannon of pharmacy text (Procter’s Practice of Pharmacy)
Medicine does not include the anal suppository and journal (American Journal of Pharmacy) were
among other dosage forms. Diepgen concluded in print; a number of colleges were established
that the lack of attention to the suppository along the East Coast and the first west of the
was because of Galen’s influence on the authors Alleghenies (Cincinnati College of Pharmacy);
(p. 13).5 This lack of attention was later evident and the American Pharmaceutical Association
in Hildegard von Bingen’s Causae et Curae, pub- was formed (1852) in response to the need for
lished in the twelfth century. improved standards.
Diepgen noted that the suppository gained In 1847, Friedrich Mohr published a treatise
some notoriety from the twelfth-century Masters in German that he intended to be a com-
of Salerno. Salerno, one of the earliest medical prehensive work on pharmaceutical technology
schools, is considered important because of the for pharmacists, chemists, chemical manufac-
many surviving texts. Roger Frugard, one of turers, and physicians.7 Significantly, there is
the Salerno figures, was the first to separate the no mention of suppositories in his work, im-
terms “suppository” for anal use and “pessary” plying that this dosage form was not a signif-
for vaginal use. Among the uses for suppositories icant item for apothecaries in Germany at the
were bowel cleansing, especially in the fevered time.
patient, psychosis, colic, and hemorrhoids In 1849, Theophilus Redwood, one of the
(p. 15).5 founding fathers of the Pharmaceutical Society
The form, content, and manner of preparation of Great Britain and the first Professor of Phar-
of suppositories changed little over the centuries. macy in the Society’s own school of pharmacy,
The form was frequently a plug or ball of materi- translated and greatly expanded Mohr’s book.
als that could be inserted in the anus or vagina. Redwood added a description of suppositories
Soap, wax, lard, and suet were used as a base noting that they were:
for additional ingredients and to provide shape.
An alternative format was the use of a cloth, a form of medicine now very rarely adopted. It
or lint, with medicament spread on it prior to is intended for the administration of medicinal
insertion. The medicaments included much of agents to the rectum. The ingredients are made
the materia medica of the period and were usually into a paste, which is usually rolled into a conical
intended either to act as bowel cleanser or to form, like a pastil. Soft soap or grease is generally
provide a systemic effect, such as narcotics. The used as the excipients for giving the required
turning point in the production of suppositories consistence to suppositories (p. 363).8
began as early as 1701 when Wilhelm Homberg
first prepared cocoa butter by pressing heated Later that same year, William Procter, Jr, Pro-
cocoa beans, and continued in 1779 when Carl fessor of Pharmacy at the Philadelphia College
Wilhelm Scheele discovered glycerin. However, of Pharmacy enlarged the book, editing it for
these discoveries did not pass into common a North American audience. However, Procter
practice until the mid-nineteenth century. retained Redwood’s comments regarding suppos-
itories with no changes (p. 515).1 This was not
an oversight since Edward Parrish, also on the
faculty of the Philadelphia College of Pharmacy
Modern period
and principal of the Philadelphia School of Prac-
tical Pharmacy, in the first textbook written by
While it is difficult to determine the exact date an American for an American audience, noted in
of the arrival of the modern period in pharmacy, 1856:
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

16 Suppositories

Suppositories as a class of medicine, are so seldom nor uniform suppositories. The earliest metallic
prescribed, that I can lay claim to little practical suppository molds in America were impressions
familiarity with their preparation. They are used in the shape of a suppository in a metal block
to insert into the rectum to fulfil [sic] several or a tin tray. In 1864, William Chapman of
indications; sometimes their action is mechan- Cincinnati, an early president of the American
ical, but they usually owe their utility either to Pharmaceutical Association, made the molds and
a narcotic, astringent, or cathartic ingredient (p. sold them to pharmacists for $5.00.13 By the
452).9 1870s a number of US patents were granted for
suppository molds including the Spenzer model
In spite of the disclaimer of lack of familiarity, that was divided to facilitate removal of the
Parrish goes on to note that there is an official pill finished product (Figure 2.1). In 1871, Henry
preparation in the United States Pharmacopeia, B. Brady, president of the British Pharmaceuti-
Pilulae Saponis Compositae, which contains opium cal Conference, exhibited a set of suppository
and soap, is formed into a mass, and, after it molds at the American Pharmaceutical Associa-
has been smeared with a bland oil, is inserted tion meeting in St. Louis. The molds were de-
into the anus either with the finger or tube scribed as exquisite, gun-metal and silver-plated,
insertion. Parrish also cites a landmark paper in with form sizes ranging from 15 to 120 grains,
the American Journal of Pharmacy by Alfred Taylor. and costing $125 for the set.13
Pharmacist Alfred B. Taylor of Philadelphia In 1868, Alexander Knowlson patented the
reported that there was no information in the first mold to use compression to form the
National Dispensatory on the valuable class of suppository, but the first successful mold was
medicinal applications (suppositoria) in spite attributed to Henry Heyl in 1879 (Figure 2.2).11
of their long use in France. He cited François Its importance for the compounding pharmacist
Dorvault’s L’officine, ou, Répertoire Général de Phar- has been described:
macie Pratique which included the use of cocoa
butter as a suppository vehicle and formulas for In this progressive age, when the requirements
anthelmintic, anti-hemorrhoidal, astringent, em- of the medical profession demand the greatest
menagogue, laxative, and vaginal suppositories amount of exactness, nicety and expedition on
containing active ingredients such as belladonna, the part of the dispensing chemist, we notice
calomel, and quinine. Taylor also provided for- that Mr. H.C. Archibald, pharmacist, No, 4099
mulas from Samuel Gray’s Supplement to the Lancaster avenue, Philadelphia, has come to the
Pharmacopeia (London) that were originally taken relief of the latter by the invention of a machine
from the 1845 Codex Medicamentarius Hamburgen- which will (and ought to) revolutionize the
sis. Of particular interest to the American reader present tedious, and to some extent inaccurate
were directions on how to make a suppository way of preparing suppositories, and be hailed
using cocoa butter and the inclusion of two for- with delight by those who are required to furnish
them almost daily.14
mulas for opium suppositories used by American
physicians using the fusion method.10 In 1875 the question of preference for the various
types of suppository molds was addressed at
the American Pharmaceutical Association annual
meeting. The “opinions of a large number of
Suppository molds
our most intelligent pharmacists throughout the
Eastern, Middle, and Western States” were re-
As pointed out by Griffenhagen in his history ported by Richard Mattison. The cold or compre-
of the suppository mold, the introduction of sion process was compared to the melting process
cocoa butter brought the need for suppository with 19 different molds. The Knowlson mold
molds to the fore.11,12 While Taylor and others for rectal, vaginal, and urethral suppositories was
recommended the use of a paper cone placed the preferred machine and one of its benefits
in a box of sand to provide support, this ap- was that the youngest apprentice could turn out
proach provided neither ease of compounding as good suppositories as the skilled pharmacist
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

Chapter 2 • History and development of the suppository 17

Figure 2.1 Drawings of the Spenzer suppository mold described in U.S. Patent #142,524, patented September 2, 1873.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

18 Suppositories

Figure 2.2 Drawings of the first successful compression suppository mold described in U.S. Patent 214,775 patented
April 29, 1879, by H.R. Heyl.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

Chapter 2 • History and development of the suppository 19

(Figure 2.3). The preferred mold for the melting Pharmacopeia (USP). The 1867 edition of the
process was one manufactured by Benton, Myers, BP added cocoa butter to the formulas for the
& Cranfield. Mattison noted that some pharma- original two suppositories and added Suppositoria
cists avoided the melting process because of the Hydrargyri and Suppositoria Plumbi Composita.20
potential for the active ingredient to separate and In the 13th edition of the USD in 1876 the
pool at the apex of the suppository and editori- convenient weight for suppositories is reported to
alized “that in the hands of pharmacists [italics be 25 grains with the added note that the BP stan-
in original] such evidences of unpharmaceutical dard, based on Henry Brady’s recommendation,
skill never occur.”15 In 1897 Whitall, Tatum was 15 grains.21 An expanded footnote discussed
introduced the “No. 3 Suppository Machine” the medicated pessaries and their resemblance to
which eventually became the preferred mold for suppositories. This footnote was continued and
use in the pharmacy16 (Figure 2.4). expanded in the 14th edition in 1880 with infor-
mation on medicated bougies and urethral and
vaginal suppositories. Also in the 14th edition,
the suggested weight for suppositories for infants
Official status
and children was provided (5–10 grains).22 There
were formulas for 12 suppositories. By 1883 there
The first mention of oil of theobroma in the were numerous formulas for suppositories in
United States Dispensatory (USD) appeared in the Martindale’s Extra Pharmacopoeia.23
“Drugs and medicines not officinal” Appendix in Glycerin was originally added to the 1850 USP.
the 1834 edition (p. 1079).17 The use given for Used mainly as a vehicle for topical medications,
cocoa butter was in cosmetic unguents although there had been some attempts to use it internally
it was not listed in any formula. The first listing of as a replacement for cod liver oil and even as a
suppositories did not occur until the 1854 edition sweetening agent for diabetics.24 In 1890 glycerin
and, while soap was identified as the common suppositories were added to the USP.25 During
ingredient, Taylor’s recommendation of cocoa the annual American Pharmaceutical Association
butter was cited. However, the information on meeting in 1892, Joseph Remington responded to
the use of cocoa butter did not expand to include a query on the best way to manufacture glycerin
suppositories until the 11th edition in 1858. suppositories, which were used as laxatives.26
In 1866 the USD added suppositories to Part Glycerin had not been considered an ideal ve-
II (preparations) and greatly enlarged the entry. hicle for other medications.
The entry stated that “they [suppositories] would
seem to have a claim to this position quite as
strong as the Enemata, which have long been
Commercial manufacturing
officially recognized (p. 1361).”18 This addition
was due, at least in part, to the appearance of sup-
positories as officinal preparations in the British By the end of the nineteenth century machines
Pharmacopoeia (BP). The entry noted that the had been developed to mass-produce supposito-
BP only had two suppositories (Suppositoria Acidi ries. At the 1893 annual meeting of the American
Tannici and Suppositoria Morphiae19 ); this was not Pharmaceutical Association, Henry Wellcome
meant to be limiting but rather to provide a noted that the shape of the suppository had
pattern for other formulas. In describing the remained the same ever since the introduction
shape and weight of the ideal suppository, the of the dosage form. Although the shape was
entry also suggested that a hollow could be made easy to insert, it was equally easy to expel.
in a preformed suppository, an active ingredient He reported the development of a new shape
placed in the hollow, and the depression closed with a “thick bulb abruptly pointed at the apex
with additional cocoa butter. Another reason for like a fat cigar or minie bullet, and gradually
the expanded information on suppositories was tapered at the base.”27 A patent by Charles Trusler
the statement that provision was made for Oil in 1897 claimed that his invention overcame
of Theobroma to be added to the United States some of the production problems evidenced by
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

20 Suppositories

Figure 2.3 Drawings of A.M. Knowlson Suppository Machine described in U.S. Patent 79,840 patented July 16, 1805.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

Chapter 2 • History and development of the suppository 21

Figure 2.4 Drawings of the Tatum Suppository Machine, described in U.S. Patent 536,240 patented March 26, 1895.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

22 Suppositories

Figure 2.5 Pages from a Wyeth catalog depicting the various rectal, vaginal, uterine, urethral, nasal and aural-shaped
molds they had available for purchase.

earlier equipment.28 Griffenhagen noted that such as opium, morphine, cocaine, belladonna,
John Wyeth & Brothers began mass manufactur- and atropine, the firm offered to manufacture
ing and advertising of suppositories at least as special formulas within a few hours and upon
early as 1870.11 In the 1901 catalog, Wyeth lists reasonable terms (Figure 2.5).29 Most other major
18 different mold sizes and shapes for rectal, vagi- manufacturers of the period also manufactured
nal, uterine, urethral, nasal, and aural supposi- and sold a broad line of suppositories.
tories and an additional eight for glycerin sup- Hollow suppositories were designed to take ad-
positories. In additional to the pre-manufactured vantage of mass production to ease pharmacists’
items containing numerous active ingredients, compounding. As early as 1881 Hall & Ruckel
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

Chapter 2 • History and development of the suppository 23

Figure 2.5 Continued

Wholesale Druggists of New York City advertised hollow forms was as great as manufacturing
a complete line of hollow suppositories made the entire suppository. In addition, no effect
from cocoa butter. The pharmacist could add any was realized until the suppository was melted,
medicine as long as it was cold and insert the unlike suppositories with the medicament evenly
plug at the back end of the suppository before dis- distributed throughout.30 In 1885, Remington
pensing. However, these did not gain widespread noted the recommendation to use gelatin shells
use since the labor in preparing and filling the having conical caps as suppositories; however,
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

24 Suppositories

this did not appear to gain any significant to depend on the medicine, its solubility, its
following.31 availability, and its effectiveness for the purpose
In 1937 Bird reported preliminary experiments intended.33
with a new suppository base, propylene glycol It is not the role of the historian to predict
stearate.32 He noted a number of advantages the future. The future role of the suppository
that the excipient provided when used in sup- will depend largely on the need of medicaments
positories, including its stability and ease of to be delivered through the body’s orifices and
shaping. Preliminary data indicated that water- the ability to deliver them in a safe and effective
soluble medicines were easily absorbed from the manner. Indeed, the future belongs to researchers
vehicle. and clinicians; the historian will follow behind to
record their efforts.

Summary
References
Since the 1850s a focus in the history of sup-
positories has been on whether they worked.
1. Mohr F, Redwood T. Practical Pharmacy: the Arrange-
This question was applied at two different levels.
ments, Apparatus, and Manipulations of the Pharma-
The first was whether the suppository worked
ceutical Shop and Laboratory. Edited, with extensive
for the compounding pharmacist or manufac- additions, by William Procter, Jr. Philadelphia: Lea
turer. The second was whether it worked for the and Blanchard, 1849.
patients.
Beginning with Taylor in 1852 the question 2. Parrish E. An Introduction to Practical Pharmacy.
Philadelphia: Lea and Blanchard, 1856: 452.
posed was how to make suppositories that would
accept the addition of the medicinal agent, how 3. Sweringen HV. Pharmaceutical Lexicon: A Dictionary
it could be formed, and how it could be packaged of Pharmaceutical Science. Philadelphia: Lindsay &
and dispensed. The underlying assumption was Blakiston, 1873.
that if the suppository vehicle could be formed, 4. Dunglison R. Medical Lexicon: A Dictionary of Med-
medicines that were effective orally would also ical Science, new edition revised by Richard J
be effective rectal or vaginally. Since many of the Dunglison Philadelphia: Henry C. Lea, 1874: 1002.
active ingredients were intended to cause evacu-
5. Diepgen P. Das Analzäpfchen in der Geschichte der
ation, provide a topical astringent or demulcent
Therapie. Stuttgart: Georg Thieme Verlag, 1953 [all
effect, or deliver an analgesic, this assumption references, including pagination, are to the English
was reasonable. The secondary literature, such as translation The Anal Suppository in the History of
Scoville’s Art of Compounding and Remington’s Therapy, translated by Lowenberg, Georgia Carole].
Practice of Pharmacy, focused more on formulas
6. Bryan CP. The Papyrus Ebers D. New York: Appleton
and physical chemistry than on the question
and Co., 1931.
of effectiveness. Moreover, suppositories were an
alternative, secondary to oral administration, for 7. Mohr F. Lehrbuch der pharmaceutischen Technik: für
any systemic therapeutic action. Apotheker, Chemiker, chemische Fabrikanten, Aerzte
By the mid-twentieth century, with the ad- und Medicinal-Beamt. Braunschweig: F. Vieweg,
vent of new bases and medications, questions 1847.
were again raised about the effectiveness of the 8. Mohr F, Redwood T. Practical Pharmacy: the Ar-
suppository dosage form. The focus was whether rangements, Apparatus, and Manipulations of the Phar-
the suppository was delivering medication to maceutical Shop and Laboratory. London: Taylor,
the patient in an effective fashion. Instead of Walton, and Maberly, 1849.
assuming activity based on other dosage forms 9. Parrish E. An Introduction to Practical Pharmacy:
it became important to show absorption, blood designed as a Text-book for the Student and as a Guide to
levels and concentrations to prove effectiveness. the Physician and Pharmaceuticist. Philadelphia: Lea
Finally, the selection of the dosage form had and Blanchard, 1856.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

Chapter 2 • History and development of the suppository 25

10. Taylor AB. Suppositories. Am J Pharm 1852; 24: 18– 22. Wood GB, Bache F. The Dispensatory of the United
20. States of America, 14th edn. Philadelphia: J.B. Lip-
pincott and Co., 1868: 1466–1470.
11. Griffenhagen GA. History and evolution of the
suppository mold. Am J Pharm 1953; 125: 135– 23. Martindale W. The Extra Pharmacopoeia of Unofficial
142. Drugs and Chemical and Pharmaceutical Preparations.
London: H.K. Lewis, 1883
12. Griffenhagen G. Tools of the apothecary: 4. Suppos-
itory molds. J Am Pharm Assoc Pract Pharm Ed 1956; 24. King J. The American Dispensatory with
17: 402–403. Supplement by John King and John U. Lloyd,
17th edn. Cincinnati, Ohio: Valley Co., 1895:
13. Lloyd JU. The Chapman Suppository Mold. Proc Am
395.
Pharm Assoc 1905; 50: 501–504.
25. Pharmacopeia of the United States, Seventh Decennial
14. Ellis ET. A new method of making suppositories. Am
Revision. Philadelphia: J.B. Lippincott Co., 1893:
J Pharm 1879; 51: 184–186.
386.
15. Mattison RV. On suppository molds. Proc Am Pharm
26. Remington JP. On the preparation of glycerin
Assoc 1875; 23: 625–627.
suppositories. Proc Am Pharm Assoc 1892; 40:
16. Tatum CA. Suppository machine. US Patent 267–268.
536,240, March 26, 1895.
27. Wellcome HS. An improved shape for suppositories
17. Wood GB, Bache F. The Dispensatory of the United and bougies. Proc Am Pharm Assoc 1893; 41: 103–
States of America, 2nd edn. Philadelphia: J.B. Lip- 104.
pincott and Co., 1834 [“Officinal” was defined as
28. Trusler CL. Suppository machine. US Patent
those medicines designated in either the United
580,021, April 6, 1897.
States Pharmacopeia or the British Pharmacopoeia.]
29. Wyeth J. An Epitome of Therapeutics. Philadelphia:
18. Wood GB, Bache F. The Dispensatory of the United
John Wyeth & Brother, 1901: 126–142.
States of America, 12th edn. Philadelphia: J.B. Lip-
pincott and Co., 1866. 30. Scoville WL. The Art of Compounding, 2nd edn.
Philadelphia: P. Blakiston, Son & Co 1897: 171–
19. British Pharmacopoeia London. Printed for the Gen-
172.
eral Medical Council by Spottiswoode & Co., 1864:
338–339. 31. Remington JP. The Practice of Pharmacy. Philadel-
phia: J.B. Lippincott Co., 1885: 986.
20. British Pharmacopoeia London. Printed for the Gen-
eral Medical Council by Spottiswoode & Co., 1867: 32. Bird JC. A new suppository base. J Am Pharm Assoc
307–308. 1937; 27: 475–479.

21. Wood GB, Bache F. The Dispensatory of the United 33. Eiler JJ. Suppositories. In: Lyman RA (ed.) American
States of America, 13th edn. Philadelphia: J.B. Lip- Pharmacy. Philadelphia: J.B. Lippincott Co., 1945:
pincott and Co., 1867: 1424–1426. 374.
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:15

26
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:16

3
Suppository bases and their
characteristics

LIKE OINTMENT BASES , suppository bases play an is clear. Below the clear melting point, release
important role in the release of the medication is insignificant. At the clear melting point and
they hold and hence in the availability of the above, the rate of release increases enormously,
drug for absorption for systemic effects or for and the rate of diffusion reaches the values of a
localized action. Of course, one of the first corresponding aqueous solution. Excipients with
requisites for a suppository base is that it should great melting intervals are less favorable than
remain solid at room temperature but should those with small melting intervals.
readily soften, melt, or dissolve at body temper- 3 Release of a drug soluble in fat-like bases is
ature so that the drug it contains may be made relatively little affected by the melting state. Only
fully available soon after insertion. Certain bases occasionally, an evident increase was observed
are more efficient in drug release than others. after reaching the clear melting point. On the
For instance, cocoa butter (theobroma oil) melts whole, however, much less drug is released per
quickly at body temperature, but because the unit of time than by a drug which is insoluble
resulting oil is immiscible with body fluids, fat- in the suppository base. In contrast to a drug
soluble drugs tend to remain in the oil and have insoluble in fatty base, release of a drug soluble
little tendency to enter the aqueous physiologic in such an excipient is markedly influenced by
fluids. For water-soluble drugs incorporated in co- hydrophilia, the release being slowed down as
coa butter the reverse is usually true, and good re- the hydroxyl number increases.
lease results. Fat-soluble drugs seem to be released 4 Water-soluble bases always release the drug
more readily from water-soluble bases such as less quickly than fatty bases, independently of
polyethylene glycol (PEG) or glycerinated gelatin, the melting state.
both of which dissolve slowly in body fluids.
5 Consequently, a fat-like base should have: a
When irritation or inflammation is to be relieved,
clear melting point not exceeding about 36.5◦ C,
as in the treatment of anorectal disorders, cocoa
as small a melting interval as possible, and as
butter appears to be the superior base because of small an hydroxyl number as possible.
its emollient or soothing, spreading action.
In 1958, Eckert and Muhlemann summarized 6 Finally, for practical purposes it results that
the following concerning bases and drugs for when a quick effect is required, a fatty base
suppositories.1 should be used in which the drug is insoluble
and in which the drug must be incorporated in
1 If a drug dissolves in the suppository base, the form of a suspension. If the effect is to be
release and intestinal absorption are much slower delayed, however, a base should be chosen in
and more continuous than in the presence of a which the drug is soluble.
suspension.
2 Release of a drug insoluble in a fat-like suppos- Classification of suppository bases
itory base, but soluble in water, depends in the
first place upon the melting state and the interval
between the moment when the specimen begins Three categories of suppository bases are usu-
to expand and the moment the melted mass ally described. The first category is the fatty,

27
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:16

28 Suppositories

Table 3.1 Melting ranges of some suppository bases

Base Composition Melting range (◦ C)

Cocoa butter Mixed triglycerides of oleic, palmitic, stearic acids 34–35

Cotomar Partially hydrogenated cottonseed oil 35
Dehydag Hydrogenated fatty alcohols and esters
Base I 3–36
Base II 37–39
Base III Also contains glycerides of saturated fatty acids C12–C16 9 ranges
Fattibase Triglycerides from palm, palm kernel, and coconut oils with 35.5–37
self-emulsifying glyceryl monostearate and polyoxyl
stearate
Hexaride Base 95 33–35
Hydrokote 25 Higher melting fractions of coconut and palm kernel oil 33.6–36.3
Hydrokote 711 Same as above 39.5–44.5
Hydrokote SP Same as above 31.1–32.3
Polybase A homogeneous blend of PEGs and polysorbate 80 60–71
S-70-XX95 Rearranged hydrogenated vegetable oils 34.4–35.6
S-070-XXA 38.2–39.3
Suppocire OSI Eutectic mixtures of mono-, di-, triglycerides derived from 33–35
natural vegetable oils, each type having slightly different
properties
Suppocire OSIX 33–35
Suppocire A 35–36.5
Suppocire B 36–37.5
Suppocire C 38–40
Suppocire D 42–45
Suppocire DM 42–45
Suppocire H As above but with the addition of poly-oxyethylated glycerides 36–37.5
Suppocire L 38–40
Tegester Specially prepared triglyceride bases:
Triglycerides
TG-95 32.2–34.5
TG-MA 34.5–36.0
TG-57 34.0–36.5
Tween 61 Used alone or in combination with PEG sorbitan monostearate 35–49
Wecobee FS Triglycerides derived from coconut oil 39.4–40.5
Wecobee M 33.3–36
Wecobee R 33.9–35
Wecobee S 38–40.5
Wecobee SS 40–43
Wecobee W 31.7–32.8
Witepsol (Selected Triglycerides of saturated fatty acids C12–C18 with varied
examples) portions of the corresponding partial glycerides
H5 35.2
H12 32–33
H15 33–35
H19 34.8
H85 42–48
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:16

Chapter 3 • Suppository bases and their characteristics 29

oleaginous, or oil-type bases that melt at body

temperature to release their medication. The sec- Table 3.2 Considerations in active ingredient and
ond contains the water-soluble or water-miscible suppository base compatibility
bases and includes polymer glycol substitution
products (PEG, poloxamer), surface acting agents,
and glycerin gelatin bases that absorb water 1. Organoleptic Odor
and dissolve to release the medication. The properties Color
third group of bases is the miscellaneous group 2. Physical Boiling point
properties Clouding point
containing disintegrating agents, natural gums,
Crystalline form
effervescent agents, collagen, and others.
Density
Granulometry (particle size)
Ionization
Desirable characteristics Melting point
pH and buffer capacity
A suppository base should be physically and Solubility
chemically stable, non-irritating, non-toxic, non- Solvent properties
sensitizing, chemically and physiologically inert, Surface tension
compatible with a variety of drugs, stable during Vapor pressure or volatility
storage, and esthetically acceptable (free from Viscosity
objectionable odor and a pleasing appearance). 3. Chemical Analytical methods
It should contract slightly on cooling to release characteristics Behavior in the presence of
itself from the mold without requiring mold water, surfactants, fatty acids,
lubricants, have wetting and emulsifying prop- preservatives, etc.
erties, have a high water number and be easy Formula developed
to manufacture by molding by hand, machine, Incompatibility (metals, heat,
compression, or extrusion. It should melt or light, etc.)
dissolve in rectal fluids and should not bind or Molecular weight
otherwise interfere with the release or absorption Radical reactivity
of drug substances. Stability to hydrolysis or
oxidation
Other desirable characteristics depend upon
4. Biological Stability to bacteria and fungal
the drugs to be added. For example, bases with
properties contamination
higher melting points can be used to incorporate
Toxicity
drugs that generally lower the melting points of
the base (e.g. camphor, chloral hydrate, menthol,
phenol, thymol, and volatile oils) or to formulate and purity of the base, as these factors may mod-
suppositories for use in tropical climates. Bases ify the intermolecular forces. Polymorphic bases
with lower melting points can be used when should either be discouraged or used with tight
adding materials that will raise the melting points controls on variables during their preparation
or when adding large amounts of solids. Exam- and use. A number of physical, chemical, and
ples of different types of suppository bases and biological characteristics of bases and active prin-
their melting ranges are shown in Table 3.1. ciples that should be considered for compatibility
The tendency of a suppository base to ex- are listed in Table 3.2.
hibit polymorphism should be considered. When Additional characteristics of importance in
the intermolecular forces between the molecules selecting a suppository base can include the
comprising the base can be arranged in different following:2
ways, and the energy difference between the
potential structural forms is very low, the base r Acid value (acid number, acidity index): This
might be found to be polymorphic. The structure is the number of milligrams of potassium hy-
exhibited by the base may then be dependent droxide necessary to neutralize the free acids
upon temperature, solvent, handling procedure, in 1 g of oil, fat, wax, resin, balsam, or similar
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:16

30 Suppositories

organic substance of complex composition. The of bases with a low hydroxyl number (low partial
presence of free acids in oils, fats, and waxes is ester content) is indicated to minimize the risk
due primarily to the hydrolysis of the esters of of interaction with drugs that are chemically re-
which they are composed and may be caused active. Hydroxyl numbers also give an indication
by chemical treatment, bacterial action, or the of the hydrophilic properties of the base, which
catalytic action of light and heat. Generally, fresh can affect both drug release and absorption rates.
or recently prepared fatty substances contain r Solid Fat Index (SFI): This is defined as the
little or no free acids. However, upon aging,
percentage of solid glycerides in the fat mixture
the acid value increases slowly at first and more
at a certain temperature. Methods that can be
rapidly later. High acid values are not necessarily
used include dilatometry, differential thermal
an indication of rancidity since rancidity is a
analysis, and nuclear magnetic resonance (NMR)
result of air, or possibly bacteria, interacting with
spectroscopy. The SFI is important in describing
the liberated fatty acids.
the state of aggregation and the phase transition
r Iodine value (iodine number): This is the number of the fat.
of grams of iodine absorbed under specified
conditions by 100 g of oil, fat, wax, or other
substance. It is a quantitative measure of the
Fatty or oleaginous bases
proportion of unsaturated fatty acids present,
both free and combined as esters, that have the
Fatty bases are perhaps the most frequently
property of absorbing iodine. Drying oils, such as
employed for suppositories, principally because
linseed oil and the fish oils, have very high iodine
cocoa butter is a member of this group of
values, usually above 120, since they contain a
substances. Among the other fatty or oleaginous
large proportion of unsaturated fatty acids. The
materials used in suppository bases are many
non-drying oils, such as olive oil and almond
hydrogenated fatty acids of vegetable oils such as
oil, have relatively low iodine values, below
palm kernel oil and cottonseed oil. Also, fat-based
100. The semi-drying oils, such as cottonseed oil
compounds containing compounds of glycerin
and sesame oil, have intermediate iodine values
with the higher molecular weight fatty acids,
between 100 and 120. Animal fats generally have
such as palmitic and stearic acids, may be found
an iodine value less than about 90. The iodine
in fatty suppository bases. Compounds such as
value can provide information on the degree of
glyceryl monostearate and glyceryl monopalmi-
unsaturation in the substance. It is an indication
tate are examples of these types of agents. The
of resistance to oxidation and rancidity.
suppository bases in many commercial products
r Saponification value (saponification number, employ various and varied combinations of these
Koettsdorfer number): This is the number of mil- types of materials to achieve a base possess-
ligrams of potassium hydroxide required to neu- ing the desired hardness under conditions of
tralize the free acids and saponify the esters shipment and storage and the desired quality
contained in 1 g of fat, fatty or volatile oil, of submitting to the temperature of the body
wax, resin, balsam, or other substance of similar to release their medicaments. These bases gen-
composition. erally have a low water content and minimal
tendency towards hygroscopicity. These bases, if
r Hydroxyl value (hydroxyl number): This is the
not properly packaged, may develop a “bloom”
number of milligrams of potassium hydroxide consisting of powdery crystals on the surface of
equivalent to the hydroxyl content of 1 g of the suppository. This is often the result of the
the substance. It gives an indication of the high-melting-point components in the base and
identity and purity of fatty substances possessing can be overcome by using a different base or
alcoholic hydroxyl groups. Generally, bases with precrystallizing the base prior to pouring; this
a low hydroxyl number tend to be less plastic will cause the crystals to form quickly with more
than those with higher values and, when rapidly complete crystallization into the final crystalline
cooled, may become excessively brittle. The use form. This process is referred to as “tempering.”
Royal Pharmaceutical Society of Great Britain September 16, 2007 23:16

Chapter 3 • Suppository bases and their characteristics 31

In some instances, suppository bases are prepared will be useless to the patient, representing a loss
with the fatty materials emulsified or with an of time, materials, and prestige to the pharmacist.
emulsifying agent present to prompt emulsifica- Cocoa butter must be slowly and evenly
tion when the suppository makes contact with melted, preferably over a water bath of warm
the aqueous body fluids. These types of bases are water, to avoid the formation of the unstable
arbitrarily placed in the third, or “miscellaneous” crystalline form and to ensure the retention in
group of suppository bases. the liquid of the more stable ␤ crystals that will
Cocoa butter, NF, is defined as the fat obtained constitute nuclei upon which the congealing may
from the roasted seed of Theobroma cacao. Cocoa occur during chilling of the liquid.
butter, or theobroma oil, is an oleaginous base Substances such as phenol and chloral hydrate
that softens at 30◦ C and melts at 34◦ C. At room tend to lower the melting point of cocoa butter
temperature it is a yellowish white solid with a when incorporated with it. If the melting point
faint, agreeable chocolate-like odor. Chemically, is lowered to such an extent that it is not feasible
it is a mixture of liquid triglycerides entrapped to prepare a solid suppository using cocoa butter
in a network of crystalline, solid triglycerides. alone as the base, solidifying agents such as
Palmitic and stearic acids make up about half cetyl esters wax (about 20%) or beeswax (about
of the saturated fatty acids, while oleic acid is 4%) may be melted with the cocoa butter to
the one unsaturated fatty acid. Because cocoa compensate for the softening effect of the added
butter melts between 30◦ C and 36◦ C, it is an substance. However, the addition of hardening
ideal suppository base, melting just below body agents must not be so excessive as to prevent
temperature and yet maintaining its solidity at the melting of the base after the suppository has
usual room temperatures. However, because of been inserted into the body, nor must the waxy
its triglyceride content, cocoa butter exhibits material interfere with the therapeutic agent
marked polymorphism, or the property of exist- in any way so as to alter the efficacy of the
ing in several different crystalline forms. product.
Cocoa butter has four different forms – ␣, Other bases in this category include commer-
␤, ␤ , and ␥ – with melting points of 22◦ C, cial products such as Fattibase (triglycerides from
34–35◦ C, 28◦ C, and 18◦ C, respectively. The ␤ palm, palm kernel, and coconut oils with self-
form, which is the most stable, is preferable for emulsifying glyceryl monostearate and polyoxyl
suppositories. Cocoa butter will melt to form a stearate) and the Wecobee bases (triglycerides
non-viscous, bland oil. Because it is immiscible derived from coconut oil) and Witepsol bases
with body fluids, it may leak from the body (triglycerides of saturated fatty acids C12–C18
orifice. Polymorphs with lower melting points with varying portions of the corresponding par-
will eventually convert to a more stable form over tial glycerides). These additional bases, which
time. Because of this polymorphism, when cocoa make up the largest group in this category, are
butter is hastily or carelessly melted at a temper- chemically modified during their preparation
ature greatly exceeding the minimum required to produce a range of products with control-
temperature and then quickly chilled, the result lable characteristics, as described in Tables 3.3
is a metastable crystalline form (␣ crystals) with and 3.4.
a melting point much lower than the original To avoid the base sticking to the molds when
cocoa butter. In fact, the melting point may be suppositories are being prepared, the cocoa butter
so low that the cocoa butter will not solidify at must not be overheated and the molds must be
room temperature. However, since the crystalline clean and dry before use.
form represents a metastable condition, there is
a slow transition to the more stable ␤ form of
Hydrogenated vegetable oil bases
crystals, which have the greater stability and the
higher melting point. This transition may require Fattibase (Paddock Laboratories, Minnesota, USA)
several days. Consequently if suppositories that is a preblended suppository base that offers the
have been prepared by melting cocoa butter for advantages of a cocoa butter base with few of
the base do not harden soon after molding they the drawbacks. It is composed of triglycerides
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Suppository bases (Gattefossé, France) for compounding and manufacturing

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Multipurpose vehicles: interesterified

Suppocire AI Semi-synthetic USP/NF Versatile base for simple <0.50 <2 224–246 20–30 33.0–35.0
glycerides EP formulations
JPE Adapted to active ingredients
increasing the melting point
Suitable for semi-automatic and
automatic manufacturing
Suppocire A Semi-synthetic USP/NF Versatile base for simple <0.50 <2 224–246 20–30 35.0–36.5
glycerides EP formulations
JPE Suitable for semi-automatic and
automatic manufacturing
32

Suppocire B Semi-synthetic USP/NF Similar to Suppocire A, with a <0.50 <2 220–244 20–30 36.0–37.5
glycerides EP higher melting point
JPE
Suppocire C Semi-synthetic USP/NF Versatile base for simple <0.50 <2 218–242 20–30 38.0–40.0
glycerides EP formulations
JPE Adapted to active ingredients
decreasing the melting point
Suitable for semi-automatic and
automatic manufacturing
Suppocire D Semi-synthetic USP/NF Similar to Suppocire C, with a <0.50 <2 210–232 20–30 42.0–45.0
glycerides EP higher melting point
JPE
Suppocire Semi-synthetic USP/NF Versatile base suitable for all types <0.50 <2 224–246 15–25 35.0–36.5
AS2 glycerides EP of production equipment
JPE

September 16, 2007

Suppocire Semi-synthetic USP/NF Similar to Suppocire AS2, with a <0.50 <2 224–246 15–25 36.0–37.5
BS2 glycerides EP higher melting point
JPE

23:16
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Continued

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Suppocire AT Semi-synthetic USP/NF Versatile base for manual or <0.50 <2 220–244 27–37 35.0–36.5
glycerides EP semi-automatic manufacturing
JPE
Suuppocire Semi-synthetic – Versatile base. The non-ionic <0.50 <2 218–242 15–25 35.0–36.5
AS2X glycerides emulsifying additive enables
incorporation of water or
alcoholic extracts or solutions
Suppocire Semi-synthetic – Simiilar to Suppocire AS2X, with a <0.50 <2 218–242 15–25 36.0–37.5
BS2X glycerides higher melting point
Suppocire Semi-synthetic – Similar to Suppocire BS2X, with a <0.50 <2 218–242 15–25 38.0–40.0
CS2X glycerides higher melting point
Low reactivity vehicles: interesterified
33

Suppocire Semi-synthetic USP/NF Base with a low hydroxyl value to <0.20 <2 231–255 <10 33.0–35.0
AIM glycerides EP avoid interaction between free
JPE OH groups and acidic active
ingredients. Suitable for high
rate manufacturing but
shock-cooling should be avoided
Suppocire Semi-synthetic USP/NF Similar to Suppocire AIM, with a <0.20 <2 228–252 <10 35.0–36.5
AM glycerides EP higher melting point
JPE
Suppocire Semi-synthetic USP/NF Similar to Suppocire AIM with a <0.20 <2 226–250 <10 36.0–37.5
BM glycerides EP higher melting point
JPE
Suppocire Semi-synthetic USP/NF Similar to Suppocire BM, with a <0.20 <2 224–246 <10 36.0–38.0
BCM glycerides EP slightly higher melting point
JPE

September 16, 2007

Suppocire Semi-synthetic USP/NF Similar to Suppocire BM, with a <0.20 <2 224–246 <10 38.0–40.0
CM glycerides EP higher melting point
JPE

23:16
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Continued

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Suppocire Semi-synthetic USP/NF Similar to Suppocire CM, with a <0.20 <2 214–236 <10 42.0–45.0
DM glycerides EP higher melting point
JPE
Low reactivity vehicles compatible with large amounts of powders: interesterified
Suppocire Semi-synthetic USP/NF Base with a low hydroxyl value to <0.50 <3 228–252 <10 33.0–35.0
AIML glycerides avoid interaction between free
OH groups and acidic active
ingredients. The phospholipidic
additive enables incorporation
of large amounts of powders
Suppocire Semi-synthetic USP/NF Simiilar to Suppocire AIML, with a <0.50 <3 228–252 <10 35.0–36.5
34

AML glycerides higher melting point

Suppocire Semi-synthetic USP/NF Similar to Suppocire AML, with a <0.50 <3 225–249 <10 36.0–37.5
BML glycerides higher melting point
Amphiphilic suppository bases (P type)
Suppocire AP Saturated poly- – Amphiphilic suppository base that <1.00 <1 206–220 30–60 33.0–35.0
glycolysed enables solubilization and
glycerides absorption enhancement of
active ingredients
Suppocire BP Saturated poly- – Similar to Suppocire AP, with a <1.00 <1 201–215 30–50 35.0–37.0
glycolysed higher melting point
glycerides
Suppocire CP Saturated poly- – Similar to Suppocire BP, with a <1.00 <1 197–211 30–50 38.5–40.5
glycolysed higher melting point
glycerides

September 16, 2007

Suppocire DP Saturated poly- – Similar to Suppocire CP, with a <1.00 <1 180–210 25–50 41.0–45.0
glycolysed higher melting point
glycerides

23:16
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Continued

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Low reactivity vehicles: esterified

Suppocire Semi-synthetic USP/NF Bases with low hydroxyl value to <0.20 <2 230–250 <3 34.0–36.5
NA O glycerides EP avoid interaction between free
JPE OH groups and acidic active
ingredients. Suitable for high
rate manufacturing but
shock-cooling should be avoided
Suppocire Semi-synthetic USP/NF <0.50 <2 228–252 4–14 33.5–35.5
NAI 10 glycerides EP
JPE
Suppocire Semi-synthetic USP/NF 0.50 <2 228–252 4–14 34.5–36.5
35

NA 10 glycerides EP
JPE
Suppocire Semi-synthetic – <1 <2 225–240 <20 35.0–37.0
NAS 10 glycerides
Suppocire Semi-synthetic USP/NF <0.20 <2 230–240 5–15 34.5–36.5
NA 15 glycerides EP
JPE
Suppocire Semi-synthetic – <1.30 <2 220–230 5–15 37.0–39.0
NAIS 10 glycerides
Suppocire Semi-syntheticUSP/NF Versatile base for formulation <0.50 <2 245–260 7–17 37.0–41.0
NCS 10 glycerides EP adapted to active ingredients
JPE decreasing the melting point
JSFA
Large-scale production vehicles: esterified
Suppocire Semi-synthetic USP/NF Bases with a high hydroxyl value <0.30 <2 224–246 20–30 33.5–35.5

September 16, 2007

NAI glycerides EP for large-scale productions with
JPE shock-cooling and/or high
JSFA amounts of powder

23:16
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Continued

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Suppocire Semi-synthetic USP/NF <0.50 <2 230–250 <30 33.2–35.2

NAI 25A glycerides EP
JPE
JSFA
Suppocire Semi-synthetic USP/NF <0.30 <2 225–240 30–40 34.0–36.0
NA 35 glycerides EP
JPE
Suppocire Semi-synthetic USP/NF <0.50 <2 218–242 38–48 33.5–35.5
NAI 50 glycerides EP
JPE
36

Suppocire Semi-synthetic USP/NF <0.50 <2 217–239 35–45 34.5–36.5

NA 50 glycerides EP
JPE
Suppocire Semi-synthetic USP/NF <0.30 <3 225–240 40–50 34.5–35.5
NAS 40 glycerides EP
JPE
Suppocire Semi-synthetic USP/NF <0.30 <3 225–235 40–50 33.5–35.5
NAS 50 glycerides EP
JPE
Suppocire Semi-synthetic USP/NF <1.00 <3 215–230 50–65 33.5–36.5
NAS 55 glycerides EP
JPE
JSFA
Suppocire Semi-synthetic USP/NF <1.00 <1 215–245 80–100 34–36
NAIS 90 glycerides EP

September 16, 2007

JPE
JSFA

23:16
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Continued

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Multipurpose vehicles: esterified

Suppocire Semi-synthetic USP/NF Versatile base, suitable for all types <0.30 <2 225–240 20–30 34.5–36.5
NAI 25 glycerides EP of production equipment. Yields
JPE suppositories showing a high
mechanical resistance
Suppocire Semi-synthetic USP/NF Versatile base, suitable for all types <0.50 <2 224–246 20–30 34.5–36.5
NA glycerides EP of production equipment. Yields
JPE suppositories showing a high
mechanical resistance
Suppocire Semi-synthetic USP/NF Similar to Suppocire NA, with a <0.50 <2 214–236 20–30 36.5–38.5
NB glycerides EP higher melting point
JPE
37

glycerides
Suppocire Semi-synthetic USP/NF Similar to Suppocire NB, with a <0.50 <2 214–236 20–30 38.0–40.5
NC glycerides EP higher melting point
JPE
Suppocire Semi-synthetic USP/NF Similar to Suppocire NC, with a <0.50 <2 204–226 20–30 42.0–45.0
ND glycerides EP higher melting point
JPE
Suppocire Semi-synthetic USP/NF Base for suppositories showing a <1.00 <3 224–246 20–30 34.5–36.5
NAL glycerides high mechanical resistance. A
phospholipidic additive enables
incorporation of high amounts
of powder
Suppocire Semi-synthetic USP/NF Similar to Suppocire NAL, with a <0.50 <3 218–242 20–30 36.0–38.0
NBL glycerides higher melting point
Suppocire Semi-synthetic – Base for suppositories showing a <0.50 <2 218–242 20–30 34.5–36.5

September 16, 2007

NAX glycerides high mechanical resistnace. A
non-ionic emulsifying additive
enables incorpation of water or
alcoholic extracts or solutions

23:16
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Continued

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Suppocire Semi-synthetic – Similar to Suppocire NAX, with a <0.50 <3 214–236 20–30 36.0–28.5
NBX glycerides higher melting point
Suppocire Semi-synthetic – Similar to Suppocire NBX, with a <0.50 <3 214–236 20–30 38.0–41.0
NCX glycerides higher melting point
Vehicles for vaginal suppositories (pessaries)
Ovucire WL Semi-synthetic USP/NF Versatile base for vaginal <0.50 <8 215–235 43–63 32.5–35.5
2944 glycerides EP suppositories
JPE
Ovucire Semi-synthetic USP/NF Base with an emulsifying additive to <0.50 <3 215–235 40–60 32.0–35.0
38

3264 glycerides improve dispersibility and

wettability of the actives.
Fast melting at body temperature.
Forced cooling is necessary
Ovucire Semi-synthetic USP/NF Base for vaginal suppositories <1.00 <7 215–225 60–70 32.5–34.0
3460 glycerides
Specific hard fat for the Japanese market: interesterified and esterified
Japocire NA Semi-synthetic USP/NF Versatile base, suitable for all types <0.20 <2.0 235–245 <3.0 33.5.35.5
O glycerides EP of production equipment. Yields
JPE suppositories showing a high
JSFA mechanical resistance
Japocire Semi-synthetic USP/NF Excipient used to produce <1.30 <3.0 220–230 5–15 37.0–39.0
NAIS 10 glycerides EP suppositories with high crushing
JPE force

September 16, 2007

JSFA

23:16
 Royal Pharmaceutical Society of Great Britain
Table 3.3 Continued

Acid Iodine Saponification Hydroxyl

value (mg value (g value (mg value (mg Melting
Product name Composition Compendia Description KOH/g) I2 /100 g) KOH/g) KOH/g) range (◦ C)

Japocire NA Semi-synthetic USP/NF Base with a low hydroxyl value to <0.20 <2.0 230–240 <15.0 33.5–35.5
15 glycerides EP avoid interaction between free
JPE OH groups and acidic active
JSFA ingredients. Suitable for high
rate manufacturing but
shock-cooling should be avoided
Japocire DM Semi-synthetic USP/NF Base with a low hydroxyl value to <0.30 <2.5 220–230 <15.0 42.0–44.0
glycerides EP avoid interaction between free
39

JPE OH groups and acidic active

JSFA ingredients. Suitable for high
rate manufacturing but
shock-cooling should be avoided
Japocire Semi-synthetic USP/NF Suppository base with a high <0.30 <2.5 225–235 40–50 33.5–35.5
NAS 50 glycerides EP hydroxyl value suitable for
JPE large-scale productions with
JSFA shock-cooling and/or high
amounts of powder
Japocire Semi-synthetic USP/NF Excipient for vaginal suppositories <1.00 <3.0 215–230 50–65 33.5–35.5
NAS 55 glycerides EP
JPE
JSFA

Adapted from Rectal Route Excipients, Gattefossé, Cedex-France.

September 16, 2007

23:16
Another random document with
no related content on Scribd:
 — Tuon voi helposti auttaa, käyt Jullun luo ja vakuutat henkesi.

— Sen minä teen.

— Ja kirkkoherran kuoltua valitsemme sinut hänen seuraajakseen.

Pastori ei kuunnellut Jonnin viimeisiä sanoja, vaan alkoi mittailla

lattiaa, hokien myötäänsä: sen minä teen, sen minä teen —

Kummana uutisena levisi yli pitäjän tieto, että Jonni oli ostanut
Seppolan ja hankki lähteä torppariksi. Itsessään vähäpätöinen
tapaus kasvoi niin suureksi ihmeeksi, että sen edessä typerryttiin.
Suursalmen isännästä äkkiä torppariksi, kenen äly moisen ihmeen
lävitse enää voi tunkeutua, ken siitä enää löysi alkua tai loppua tai
keskikohtaa.

Jos siinä sellaisia oli olemassakaan!

Talven taittuessa kevätpuoleen kuulutettiin Jonni ja Eliina

avioliittoon. Vihkimys tapahtui kirkossa, hääsaattueessa oli nuorien
seura sekä sulhon ja morsiamen lähimmät omaiset.

Heti vihkimisen jälestä ruvettiin hommaamaan muuttoa. Martti

lupautui palvelemaan kolme vuotta Seppolan uutta isäntää ja hän
lähetettiin perille viikkoa ennen nuoren parin tuloa. Viimeisen kelin
aikoina ajoi Jonni nuorikkonsa kera Seppolan pihaan, Martti oli
tulijoita vastassa, tuvan takassa leimusi tuli ja huhtikuun aurinko
paistoi peräikkunasta lattiaan valkoisen valojuovan, johon ruskea
kissa, perintö torpan entisiltä haltijoilta, oli asettunut lepäilemään.
PIKKU ELINAN TÄHTI.

Seppola oli tavoiltaan ja naamaltaan sukunsa lajinen, mutta

riihitanhualla kasvoivat korkeat, tyviltään mustuneet ja rosottuneet
koivut, haastellen sukupolvien elämän tarinoita. Asuinrakennuksen
takana oli katajikkomäki, jonka lumi kevään tullessa ensimmäisenä
hikousi ja riensi juoksemaan mäen rinteeltä lähtevää nurmikkoa
kohti, alempana levisivät pikkupellot ja niityt, loppuen
metsäkaistaleesen, joka vasempaan suuntaan soukkeni ja työnsi
kärkensä järveen saakka. Kärjen takaa ja sen nokan sivulla siinti
järvi ja sen etäisimmällä rannalla joku talo ja talon mökki.

Seppolan asuinrakennuksessa oli vain kaksi huonetta, tupa ja pieni

kamari, johon viimemainittuun käytiin eteisestä. Ensi töiksi ruvettiin
rakentamaan kolmatta huonetta, joten rakennus venähti jonkun
kyynärän pitemmäksi. Kesällä huone valmistui. Martti sai asuakseen
pienen kamarin, isännän ja emännän hoteisiin jäi tupa,
vastarakennettu huone, joka oli tuvan jatkona, kuului aluksi
emännän käsialoihin.

Omintakeinen isännyys vaikutti Jonniin terveellisesti. Pienen torpan

oloissa täytyi hänen pilviä tavoitteleva mielensä aleta maata
lähemmäksi ja tottua pitämään silmällä käytännöllisyyttä. Joskus sai
hän maksaa oppirahojakin. Niinpä hän, vastoin Martin kiivaita
vastaväitteitä, heti ensi keväänä kylvi ostolannan kera kauraksi
muutaman uuvutetun pellonkappaleen, joka lisäksi oli
töyräsluontoinen. Kevään alkupuoli oli poutainen, kylvö ei laihassa
maassa päässyt kunnolliseen alkuunkaan, vaan kuivui ituihinsa,
mutta alavammissa ja kosteammissa maissa kasvoi kaura sakeana
kuin korpi.

— Nyt suoritit ensimmäisen maanviljelystutkintosi, nauroi Martti.

Ja mikä on tehty, ei kaipaa enää tekemistä.

Nopeaan kului ensimmäinen kesä. Oli hauskaa kiirettä aamusta

iltaan. Eliina hoiti emännän tehtävät, Martti ja Jonni touhuilivat
pelloilla ja niityillä. Ilmat oikuttelivat varsinkin loppukesällä, joten
sieti aina olla varuilla, jos mieli saada työt suoritetuiksi suunnittelujen
mukaisesti.

Pitäjälle ei Jonni enää, Seppolaan asetuttuaan, lähtenyt vierimään,

vaan ohjasi kaikki, jotka hänen apuaan tulivat pyytämään, Jullun luo,
avustaen tätä kirjeellisesti neuvoillaan, kun sattui joku piukempi
tehtävä. Ainoastaan säästöpankin johdon hän piti käsissään, se kun
oli kovin arka hoidettava.

Koko kesänä ei Seppolassa keritty lukemaan sanomalehtiä, paitse

hyvässä kaupassa sunnuntaina, jollei ollut minnekään mentävä,
mutta semmoisia sunnuntaipäiviä ilmeni harvoin. Viikolla taasen riitti
työtä joka päivä iltaan saakka, jäipä siirtojakin aamujen varalle,
vaikka päivien avuksi pantiin pientä kiirettäkin. Postinkulku sitäpaitse
oli hankala, sanomalehdet piti noutaa monen kilometrin takaa, työ,
joka tavallisesti jäi sunnuntain osalle. Noudettuja lehtiä oli siten koko
tukku, niitä oli mahdoton ennättää lukea, korkeintaan kerkisi niitä
silmäillä hätäpikaa. Mutta sattuipa sitenkin, että viikon posti jäi
kokonaan silmäilemättäkin. Silloin tuntui Jonnista omituiselta. Kun ei
tietänyt olivatko maailman asiat noin tai näin, puhumattakaan
kotimaan kuulumisista ja muista läheisimmistä, lääniä ja
paikkakuntaa koskevista kysymyksistä.

Mutta siihenkin tottui, uutisien ja tietojen kaipuu kävi vähemmän

tuntuvaksi, ajatukset alkoivat elostella vain Seppolan pelloilla ja
pientareilla, ja samalla ne alkoivat osoittaa hämmästyttävää
välinpitämättömyyttä kaikkea kohtaan, mikä oli ainetta ylempänä.
Ankara ruumiillinen väsymys lamautti mielen lennon. Joskus koetti
Jonni käyttää ruokalepoa lukemiseen, mutta heti silmäluomet
rupesivat tuntumaan äärettömän raskailta ja vaipuivat koreesti
umpeen jo kokeen alussa. Kesän kuluessa sai hän ikäänkuin esiripun
raosta tirkistää sen elämän näyttämölle, jossa hengenlahjat
kuoletetaan päivä päivältä ja vuosi vuodelta hennoimmista
lapsuusajoista saakka. Rippikoulun ajoilta muisti hän torpan poikia.
Sitä henkisen takapajun leimaa ja kypsymättömyyttä, joka
useimmiten loisti heidän kasvoistaan, vaikka silmät olivat muuten
älykkäät ja vilkkaat, sitä ei hän silloin voinut käsittää. Vasta nyt
Seppolassa, ankaran väsymyksen uuvuttaessa päivästä päivään ja
hämmästyttävän välinpitämättömyyden kasvaessa kaikkea kohtaan,
mikä oli ruumista korkeammalla, vasta nyt hän käsitti torpan pojan
kehityksen. Siinä oli kouluttajana ja vaikutuksien antajana työ, työ
kesän talven, aamun illan, työ kautta elämän hautaan asti. Ensin
työssä isän jälessä, sitte rinnalla ja sitte edellä, siinä verotorpan
pojan lapsuus, nuoruus ja miehuus —

Painui kesä syyspuoleen, tummenivat illat, tuprusi ahkeraan savu

Seppolan riihestä. Kun kaikki oli puitu ja korjattu, tehtiin tulojen
yhteenlaskut. Numerot olivat masentavia, sommitteli niitä miten
tahansa, aina jäi tulokseksi, että maanantimet jyvineen, korsineen ja
kaikkineen kipin kapin riittävät heidän elääkseen seuraavaan
uutiseen.

— En voi tätä käsittää, virkkoi Jonni rengilleen. En tarvitse maksaa

vuokraa, kun torppa on omani, mutta edeltäjäni maksoi vielä
verotkin. En käsitä, miten voitiin tulla toimeen.

— Minäpä käsitän, pantiin kitua toimeentulon rinnalle.

— Selitähän se tarkemmin.

— Kyllä selitän. Näes, kuu keitettiin kahvi, pantiin sikurin

höysteeksi vain pari papua jaloa viljaa, tupakkiin leikattiin
pyörtänekärsämön kukkia muka hauskan hajun vuoksi, jokainen
voinaula, jokainen muna vietiin kaupungin torille. Ja sinne vietiin
vasikat, porsaat ja kananpojat, sinne vietiin teeret ja metsot, joita
väsymätön mies syysaamuin pudotteli kuvilta ukkovaarin vanhalla
luotipyssyllä, sinne vietiin kaikki, mikä vain kykeni lantiksi
muuttumaan.

— Ja mitä jäi heille itselle?

— Jäi jouluksi silavaa, kesäksi kirnumaitoa ja järven kaloja.

— Muistan tämän talon entisen isännän aina ajaneen kirkolle

hyvällä hevosella.

— Sillä oli silkkimusta. Mutta kylläpä kerrotuinkin, että hän,

kyntäessään näitä peltoja silkkimustallaan, itse työnsi aatraa, jotta
selkä oli mykkyrässä.

Jonnilta pääsi nauru, mutta hän heti katui sitä.

 — Ei sopisi nauraa, koetti hän puhdistautua. Ei sopisi.

— No, ei ole itkunkaan syytä. Toimitithan itse täällä

perukirjoituksen ja huutokaupan, rahoja tuli riski tuhat, toinen sen
verta kuuluu olevan säästöjä.

— Kyllähän niin, mutta ajattelehan myöskin, että niiden eteen on

ponnisteltu koko miehuuden elämä.

— Koko miehuuden elämä kyllä, mutta ajattele myöskin, että mies

oli oma herransa, kun vain kykeni vuokran suorittamaan. Ajattele
kun hän silkkimustallaan ajoi Seppolan tanhualle ja silmäili alas
järvelle päin. Laihot olivat hänen laihojaan, hän alotti leikkuun milloin
tahtoi, hän nousi ylös ja meni makuulle milloin tahtoi, hän lähti
kuville teeriä ampumaan milloin tahtoi, hän teurasti vasikkansa ja
lähti kaupunkiin milloin tahtoi, hän oli Seppolan isäntä ja
semmoisena miehen veroinen yhtä hyvin kuin joku toinenkin. Siitä
ihmisen henki vasta elää ja sen vuoksi hän antaakin kaikki alttiiksi
sielua myöten, kun vain pääsee riippumattomaksi maatilkun
omistajaksi.

— Onhan tuo niinkin. Luuletko Seppolan minun käsissäni

ruokkivan väkensä?

— Sen se tekee jo vuotena kolmantena ennenkuin palvelusaikani

loppuukaan, ja sitte tuonnempana se kasvaa hintansa korotkin,
kunhan kaikki joutilaat nurmet, aitovarret ja ojaäyräät palkataan
työhön muiden mukaan.

Valoisan ajan mentyä ohi ja iltojen venyttyä pitemmiksi, ruvettiin

Seppolassa tarkemmin seuraamaan maailman tapahtumia. Toisen
veistellessä tai sahatessa luki toinen ääneen ja Eliinakin silmäili
lehtien viivanalaisia rakkausjuttuja tai kuunteli pääkirjoituksia ja
aikakauslehtien vakavampia selontekoja, joita Jonni aina hankaili.

Talventulo oli uutuus, koko Seppolan elo ja elämä muuttui kuin

taikalyönnillä.

— Nyt luistaa jo reki, virkkoi Martti, kun oli puolituntisen heitellyt

lumia, virkkoi ja riensi ulos, silasi harmajan ja ajoi hakemaan
sanomalehtiä.

Seuraavana päivänä ajoi Eliina kotiinsa järven jäitä ja niittyjä pitkin

ja toi Seppolaan siskonsa Naimin.

Aika riensi, läheni joulu, saapuen perille kuutamon ja helkkyvän

pakkasen kera, jotka vain kohottivat tunnelmia. Seppolan tuvan
lattialle oli levitetty olkia, liedessä leimusi hulmuisa pystyvalkia, Eliina
kattoi pöytää siskonsa kera. Kuului tanhualla kulkusien ääni. Martti
ryntäsi ulos, Jonni aikoi seurata jälessä, mutta tuvan ovi jo avautui ja
sisään astui mustiin ja suruharsoon puettu rouva, taluttaen kädestä
pientä, kahdeksan tai seitsemän vuoden vanhaa tyttöä. Ensi
hämmästyksen mentyä ohi, tunsi Jonni tulijan Jullun äidiksi.
Vaihdettiin tervehdykset ja toivotettiin iloista joulua. Istuttuaan
pystyvalkean ääreen lämmittelemään, virkkoi rouva:

— Jopa olette muuttuneet sitte viime näkemän, mutta semmoinen

te yleensä olette, jommoiseksi olen ajatuksissani kuvitellutkin teitä
Jullun kuvauksien perusteella. Tahdoin kuitenkin nähdä teitä. Mitä
minä nyt tunnen teitä kohtaan, sitä voitte vaan aavistaa.

Rouvan katse suli pehmeäksi ja ääni värähteli, mutta kasvot

loistivat valkeata mieltä.
 — Sallitteko että sinuttelen teitä molempia? Kutsukaa te minua
tädiksi.

— Kernaasti, vastasi Jonni.

Martin ja Jullun ehdittyä tupaan, käytiin jouluillalliselle.

— Eikö kenenkään uteliaisuus herää kysymään, miten minä näin

yksin kuljen, kysyi rouva.

— Epäilykseni ovat heränneet, vastasi Jonni.

— Minun myös, lisäsi Eliina. Täti on leski.

— On se kai nähty lehdissäkin.

Seppolaiset katsoivat kysyvästi toinen toisiaan silmiin. Vihdoin

Martti tunnusti:

— Minä kyllä näin, mutta satuin unhottamaan.

— Kuolema tuli aivan äkkiä. Vainaja istui keinutuolissa ja poltteli

piippuaan, puhe oli käymässä Jullusta. Hän tuumaili huomispäivänä
kirjoittaa Jallulle ja pyytää kotiin joulua viettämään. Huomenna
kirjoitan, ne olivat hänen viimeiset sanansa, ne sanottuansa pudotti
hän piippunsa ja makasi keinutuolissa hengetönnä.

-— Entä tämä pieni eläjä, kuka hän on?

Rouva silitti tytön kiharoita ja virkkoi:

— Liisillä on oma tarinansa, kun uni-Matti kerkii tupaan, sitte Liisin

tarina kerrotaan.
 Jouluillallinen päätettiin virrellä.

— Olen isän kodissa siihen tottunut, lausui Jonni, enkä osaa

ajatellakaan jouluiltaa ilman jouluvirttä.

He lauloivat kaikki yhdessä. Jonnilla oli pehmeä ja matala ääni,

jossa oli kyllä tunnetta ja sydämmellisyyttä, mutta hänen kookas
vartalonsa vaikutti, että äänen kokonaisvaikutus oli vallan erityinen,
melkein samanlainen, kuin olisi valtava koski lorissut pienen puron
lailla.

Valvottiin yötä myöhään, vihdoin Eliina virkkoi:

— Minne teemme tädille sijan?

— Tähän lattialle.

Jullu ja Liisi nukkuivat jo raskaasti, kun rouva alkoi kertoa

viimemainitun pikku tarinaa. Tyttö oli isätön, äiti oli joutunut
naimisiin viinaan menevän ja kierosilmäisen suutarin kanssa. Asuivat
kivenheiton päässä heistä. Naimisiin mennessä oli mies vannonut
julkiset valat kohtelevansa Liisiä, kuten omaa lastaan. Ne valat
tiedetään. Jo vihkijäispäivän huomenissa, häähumalan uudistuttua,
potki isä tyttöä. Silmät turvoksissa ja parkuen juoksi tyttö raukka
aina rääkkäyskohtauksien jälestä heidän kyökkiinsä, jääden väliin
yöksikin, kun oli oikein suunniltaan säikähtynyt. Sitä kesti melkein
vuoden. Oli kesäpäivä, ilon päivä, illalla tuli postissa kirje Jullulta,
jossa kerrottiin, että uusi Väinämöinen oli laulanut hänet kievarista
Taivos-ukon luostariin. Postin kintereillä seurasi Liisi, hiukset hajalla,
mustelmia kasvoissa ja käsivarsissa. Jäi yöksi, jäi päiväksi, jäi heille
ainiaaksi.
 — Tahdoin pelastaa poloisen muistoksi ensimmäisestä
valontuikkeesta surujen yössä.

— Tädin ja Jullun luonteet vetävät aivan samaan, huomautti Jonni.

— Ehkä, ainakaan ei ole Jullu kovaluonteinen.

— Ei, sen mieli on hellä ja herkkä kuin kanteleen kieli.

— Huomenna lähdemme hautaamaan isää.

— Ja sitte palaatte yksissä tänne.

— Oikein arvasit. Esitin tänään Jullelle, että vuokraisimme asunnon

muualla, mutta hän ei suostu. On kiintynyt siihen ukkoon, tupaan ja
ties mihin kaikkeen. Kertoi maanneensa ensimmäisen yön vuoteella,
joka oli tehty tyhjille laatikoille. Nykyään siellä on jo vähän
kodikastakin. Jullu ehkä ansaitsee paljo.

— Paljo se ansaitsee ja ansiot kasvavat yhä. Pian aiotaan tehdä

hänestä kunnallislautakunnan esimies.

Painuivat levolle viimeisetkin valvojat. Jonni näki, miten rouva,

makuulle kallistuttuaan, otti Jullun käden molempiin käsiinsä. Hän ei
ollut saanut hyväillä eikä koskea sitä kättä monen moneen vuoteen.

Loppujouluna tuli pastori vierailemaan Seppolaan. Nuorien seuran

johto oli joutunut hänen ja uuden opettajan hoteisiin, iltaseuroja oli
pidetty ahkeraan, olipa ryhdytty tykkänään uudemmoisiin puuhiin,
nimittäin lukutupien perustamiseen kunnan kaikille tahoille. Oli
alotettu Hosun kylästä.

— Kummat kuulet, Pesähosussa on nyt lukutupa.

 — No kissan viikset, miten kesytitte miehen?

— Nuorempien tyttärien avulla. Tärppäsi oitis.

— Se oli mainiota.

— Mutta rahoista ollaan tiukalla, ei auta muu, kuin hommata

iltamia, keräyslistat eivät tuota suurin.

Puhuttiin muistakin edistyspyrinnöistä, kunnes pastori kesken

kaikkia tokasi:

— Voiko tämä elämä tyydyttää sinua? Etkö tunne toisinaan

painostusta?

— Totta puhuakseni en ole tuntenut, paitsi parina kertana, jolloin

tapasin Eliinan itkemässä.

— Ei huoli uskoa, väitti Eliina.

— Mutta se meni ohi. Syksyn ja talven rajoissa täällä tuntuu

suvantoiselta, mutta annahan, kun lyö lumet alas taivaasta, niin
ollaan kun jossakin etukaupungissa, josta milloin tahansa pääsee
suuren maailman keskukseen. Hosulaisten ja naapuripitäjäläisten
tiukukellojen ja kulkusien kilinä kuuluu alituiseen tuolta
metsänkärjen tienoilta. Eliina, mehän asumme jossakin Lontoon tai
Pariisin etukaupungissa. Eikö niin?

— Asumme hyvinkin.

— Ja meillä on naamiohuveja ja tanssiaisiakin, kuten suuren

maailman yhteydessä olevilla ihmisillä ainakin. Näes, kun milloin
Eliinan silmät eivät ole yhtä kirkkaat kuin jänönkin, niin mitä luulet
minun tekevän? Minä rupean tanssimaan. Minusta on tullut mainio
soolotanssija. Tahdotko että näytän?

— Annahan tulla.

Jonni meni ovensuuhun, asetti päähänsä lammasnahkalakin

kallelleen ja takaraivolle, sekä alkoi tanssia. Se oli alussa vain
jalkojen ja käsien heilutusta, mutta vähä vähältä siihen yhtyi vartalo,
silmät, kasvojen ilmeet, ja sitte se muuttui niin lystikkääksi ja
hullunkuriseksi, että sitä olisi maantierosvokin pysähtynyt
katsomaan. Pastori ja Naimi nauroivat aivan tukehtuakseen.

— Nyt se on tehty, nyt ovat Seppolan emännän kaikki keijukaiset

kotona, virkkoi Jonni, joka tanssiessa oli tullut Eliinan eteen.

Kevättalvella ryhdyttiin Seppolassa uuden navetan rakentamiseen.

Ja viimeisen kelin vaiheilla syntyi Jonnille tyttö, joka ristittiin äidin
mukaan Eliinaksi.

Kevätkesällä, kaupunginmatkalta palatessa, osti Jonni, emäntänsä

ja renkinsä mieltä kuulustelematta, kaksi kallista rotulehmää
muutamasta naapuripitäjän herraskartanosta, jonka omistajan
kanssa hän, ties millä tavalla, oli joutunut tuttavuuteen. Illan suussa
saapui hän kotiin lehmineen ja lehmänajajineen. Martti istui
rappusilla, Eliina kasteli kukkalavaa ja Naimi hyssytteli tuvassa pikku
Eliinaa. Nähtyään tulijat, sylkäsi Martti jalkojensa väliin, Eliina
varjosti kädellään silmiään, kuten olisi hänen ollut vaikea tuntea
tulijoita. Mutta Jonni oli innoissaan.

— Nähkääs näitä, sanoi hän komealla äänenpainolla. Tuon

suuremman nimi on Isabella, tuon toisen Amalia, molemmat lypsävät
kahdeksan yhdeksän kannua. Mitä sanot, Eliina? Mitä sanot, Martti?
 — En antaisi Tähdikkiä molemmista yhteensä.

— Enkä Punakorvaakaan.

Jonni mainitsi uudelleen kahdeksasta ja yhdeksästä kannusta.

— Eivät ne lypsä Seppolan eväillä yhdeksää kannua. Syötä niillä

turnipsit, kakut..

— Ja maito ei ole Tähdikin eikä Punikin maidon arvoista.

— Oma paras, sanoi akka, kun pellavaa perkkasi. Teit huonon

kaupan.

— Sittepä tuo nähdään.

Sinä kesänä antoi maa runsaan sadon, kasvoi kaura ja heinä,

kasvoi ruis ja kaikki mikä oli vakoon laskettu. Onni hymyili
seppolaisille tuvassa ja tuvan ympärillä. Pikku Eliinan ilmaannuttua ei
Jonnilla enää milloinkaan ollut aihetta tanssia silmän keijukaisia
kotiin, sillä emäntä oli iloinen kuin leikkivä lapsi ja onnellinen kuin
sirkka poutasäällä.

Mutta Isabella ja Amalia myytiin Kaislaan.

— Täällä haisikin jo niin ylimykseltä, ivaili Martti, kun ajajat

katosivat lehmineen Seppolan portista. Meikäläistä alkoi oikein
hävettää omissa silmissään.

Muut nauroivat, mutta Jonni näytti vakavaa naamaa.

Elettiin talvi, jouduttiin kevääsen ja kesään, vuodentulon toiveet

alkoivat näyttää harmailta. Kevätkesällä ehkäsi kuivuus
kasvullisuuden kehitystä, heinänteon alussa alkoi sataa, ensin
harvoissa ja lyhyissä kuuroissa, sitte roiskahutteli joka päivä ja
useitakin kertoja päivässä. Kävi tukalaksi suorittaa kunnolla
minkäänmoista työtä. Sen lisäksi yhtämittaiset sateet painostivat
mieltä, ilo ei ilolta tuntunut, riemu ei riemulta maistunut. Jonni
varsinkin oli masentunut. Seppolan kannattavaisuus pyöri hänen
päässään aamulla ensimmäiseksi, illalla viimeiseksi. Edellisen vuoden
runsas sato oli nostatellut hänen itseluottamustaan ja herättänyt
hänessä toivoa, että Seppola vaivojaan valittamatta hyvinkin voi
elättää asujansa, mutta toinen kesä jo horjautteli elämän koulussa
karaistumatonta luonnetta, joka lisäksi vielä oli tuliverinen ja herkkä
pilvilinnoja rakentamaan.

— Tämä vuosi vie taaksepäin, ei auta mikään, virkkoi hän

rengilleen, rukiinkylvöä alottaessaan märkään maahan.

— Vie väkisinkin, myönteli Martti. Ne olivat kevätkesän poudat,

jotka turman tekivät, sateista ollaan kyllä vahingoitta suoriuduttu.

Päivänä muutamana, Jonnin kaivaessa vastaraivattuun peltoon

ojaa, tuli Eliina hätäilevän näköisenä kaivuulle. Oli paisteenkuuro,
aurinko hymyili herttaisesti pilvien lomista.

— Mikä nyt on?

— Pikku Eliina on sairas.

Jonnilta oli lapio pudota ojaan, mutta hän hillitsi mielensä.

— Ei se toki lie mitään vaarallisempaa, elähän huoli hätäillä.

He lähtivät yhdessä Seppolan tupaa kohti.

— Tyttöhän on ollut viime aikoina virmempi tavallista.

 — Ei se ollut enää eilen illalla ja tänä aamuna oikeissa
ruuveissaan, mutta vasta tunti sitte tuli kipu piilostaan esiin.

— Elähän sentään huoli hätäillä, tyynnytteli Jonni, vaikka tunsi

selvästi, että hän itse enimmän oli tyynnytyksen tarpeessa. Usein
pikku lapset sairastavat.

Kehdosta kuului valitus Jonnin korviin jo tuvan ovea avatessa.

Posket hohtavina vaikeroi pikku Eliina, käännellen tuskissaan
päätään oikeaan ja vasempaan, ja kun se katsoi isään, oli katseessa
jotakin, tuijottavaa ja terävää.

Mitä tehdä? Mistä apu yksinäiseen metsätorppaan, ja kuka avuksi?

Kuu ja taivahan tähdet.

Välähti neuvo Jonnin mieleen.

— Käyn noutamaan äidin tänne, äiti on tottunut ja ymmärtää.

Siihen korteen tarttui Eliinakin.

— Lähde joutuin, ehdit yön seutuvissa kotiin.

Hukkaamatta enää silmänräpäystäkään lähti Jonni ajamaan

Kaislaa kohti. Toivon kipinä alkoi lämmittää pelkojen kylmettämää
mieltä ja se toivon kipinä pani kiirehtimään. Tasaiselle maantielle
saavuttua lisättiin kulun nopeutta. Hei, harmaja, juokse, harmaja,
pikku Eliinan vuoksi, juokse. Äiti kyllä keksii avun. On tottunut ja
ymmärtää. Ei ole hätikkö, näkee heti, mitä lajia kipu on. Ja ehkei
olekaan vaarallista lajia, kun niin äkkiä yltäsi. Eiköhän ne
vaarallisemmat tule vitkemmin? Hei, harmaja, juokse, harmaja, pikku
Eliinan tähden, juokse.
 Juoksi harmaja, taival lyheni ja loppui. Ja alkoi uudestaan Kaislan
rapun edessä ja päättyi puoliyön aikana Seppolan tanhualla.

Eliina kiirehti vastaan.

— Mitenkä nyt on? Onko huonommin tai paremmin?

— Ei kumminkaan, luullakseni.

Ennallaan olikin pikku potilas, ennallaan poskien hohde, silmien

tuijottava ja terävä katse, ennallaan olivat valituksetkin, jotka
huohottavan hengityksen kera työntyivät kuuluviin.

— Onko nukkunut lainkaan?

— Ei, mutta väliin valitukset väsyvät.

Pantiin etikkakääreet pikku potilaan otsalle ja annettiin joku tippa

punaista rohtoa veden kera. Ne vaikuttivat rauhoittavasti, valitukset
väsyivät, silmien tuije pehmeni.

— Jonni menköön nukkumaan ja menkää te muutkin, kyllä minä

valvon ja hoivailen, puheli Kaislan emäntä, asettuen kehdon ääreen.

Keventynein mielin paneutui Jonni makuulle, herätessään oli päivä

jo korkealla.

— Miten nyt on laita?

Eliinan ja äidin silmäys puhui totuuden.

— Nyt on huonommin.
 Päivemmällä rauhoittui lapsi, valitukset vaikeni heikommiksi,
poskien puna laimeni ja pään liikkeet herkesivät.

— Käyn hakemaan lääkäriä, virkkoi Jonni.

Lääkäriin oli neljä penikulmaa.

— Lähde pian, kehoitti Eliina.

Jonni riensi silaamaan harmajata ja oli jo nousta rattaille, kun äiti

ilmaantui estämään.

— Jätä lähtö, pikku Eliina kuolee, ennenkuin ehdit palata.

Lähtijä taipui äidin tahtoon.

Illalla kävi tuoni lujemmin käsiksi hentoon saaliiseensa. Pieni

ruumis vavahteli, kätöset puristausivat nyrkkiin, katse terästyi
läpitunkevaksi, ja silloin tällöin kuului voimaton valitus.
Neljännestunnin teki tuoni päättäjäistyötä, sitte hento ruumis
ojentihe suoraksi, kuului pitkä, voimaton valitus, ja pikku Eliinan
silmä oli sammunut ainiaaksi.

Kalpeana seisoi Jonni kehdon ääressä, äiti, Naimi ja Eliina itkivät.

Kehto nostettiin illalla Naimin huoneeseen. Yöllä alkoivat salamat

käydä, liekit kulkivat ristiin rastiin, ja toisin silmänräpäyksin oli ilma
suurena tulimerenä, jossa salamankielet sähisten välähtelivät joka
suunnalle.

Sydänyön vaiheilla heräsi Jonni. Ensi tuokiona ei hän muistanut,

mitä oli tapahtunut, mutta sitte tuonen päättäjäistyö kuvastui
kaikkine vivahduksineen hänen silmiensä eteen. Tieto, että pikku
Eliinan tuskat nyt olivat loppuneet, synnytti sanomattoman
rauhantunteen, joka, vaikka olikin hetkellinen, oli siksi luonnollinen ja
todellinen, että se työnti syrjään muut ristiriitaisemmat tunteet.
Pikku Eliina ei kärsi enää tuonen kourissa, tuo ajatus risteili yhtä
valoisana Jonnin mielessä, kuin salamat syyskesän yössä, ja siihen
ajatukseen upposi ensi hetkien suru ja katkeruus.

Hautaus aiheutti puuhia, jotka nekin osaltaan häiritsivät tunteiden

valtaanpääsemistä. Martti rupesi höyläämään kirstua, Jonni
tuppautui apumieheksi, mutta sai mestarilta lyhyen käskyn siirtyä
etäämmäksi.

— Pane harmaja aisoihin, aja kirkonkylään ja tuo väriaineita,

komenteli
Martti.

— Ja harsoa ja liinakangasta, puuttui Eliinakin komentamaan.

Pitää myöskin käydäksesi pappilassa, lukkarilassa ja…

— Ymmärrän, vastasi Jonni, suoriutuen matkaan.

Toimitettuaan kaikki hautausta koskevat seikat reilaan, meni hän

viimeksi Alpon puotiin ostamaan harsoa ja liinakangasta. Puhelu
johtui meijerin toimintaan. Jonnin ennustukset olivat käyneet toteen,
koko meijeriliike oli taantumaan käsin. Maidonmyyjät rettelöivät
pikku syistäkin. Joku nureksi maidonajon epätasaista jakoa — ja
erosi. Toinen moitti tehtävän vääryyttä maidon rasvapitoisuuden
määrittelemisessä — ja erosi. Kolmas väheksyi yleensä
maidonhintoja, väittäen hyötyvänsä vasikkain juottamisella ja
voinmyynnillä enemmän — ja erosi Aina vaan kuului moitteita ja
tyytymättömyyttä.
 — Luovuttaisin kernaasti meijerin osuuskunnalle, pyytämättä
penniäkään voittoa. Mitä arvelet? Noinkohan käy laatuun?

— Miksei käy? Ala vain kääntämään.

— Olen tylppäkielinen, en osaa esittää asiaa niin, että kukaan

viitsii kuunnella.

— Kyllä työ kielen kouluuttaa.

— Ajattelin että jos sinä… sitte tuonnempana, kun tuut

unhottamaan surusi.
 — Minähän asun erämaassa, ei minun sovi. Vasikkain juottaminen
ja voinmyynti on minullakin pisimpänä sormena suussa. Täytyypä
rientääkseni, taival on pitkä.

Ja Jonni jätti Alpon suoriutumaan meijerivaikeuksistaan miten

parhaiten taisi.

Huomisen takaa kätkettiin pieni kirstu maan poveen. Pastori puhui

ihmistoiveiden raukenemisesta, hauta luotiin umpeen ja seppolaiset
lähtivät paluumatkalle.

Sitte vasta heräsi kaipaus. Yöllä ja päivällä, aamulla ja illalla

muistui pikku Eliina mieleen. Tyhjä kehto pisti sydämmeen kuin
terävä ase, pisti jotta kipu silmänräpäyksen jälestä tuntui ohimoissa.
Viiltävimmin tuntui kipu, kun kaipuu sattui unhottumaan hetkeksi ja
sitte törmäsi äkkiä rauhaisaan mieleen jonkun ajatuskäänteen
kautta. Silloin tuntui kuin olisi puristanut henkeä ja ruumista niin
lujasti, että veri oli pysähtyä kierrossaan.

Eikä näyttänyt Seppola enää entiseltä. Se oli kuin syynalainen,

joka oli salassa ollut tuonen liittolaisena. Sille ei enää voinut hymyillä
entistä ensimmäisen rakkauden hymyilyä, sillä se oli sydämmensä
syvään suohon varistanut silloin, kuin pikku Eliinan poskilla
punaruusut lumivalkoisiksi kylmenivät.

Kului aika, päästiin tummien syksyöiden ja usvailmojen sivu

talveen, saatiin pakkasia ja tuiskuja. Virkeni veri, elpyi ajatus
nousemaan surusta. Eräänä iltana palasi Jonni kirkonkylästä. Oli ollut
pankkipäivä. Aamulla tuiskutteli, mutta iltapuoleen seesti ja laati
pakkasen. Näkyivät tähdet, näkyi kuu. Kotitaivalta tehdessä
ajautuivat Jonnin ajatukset tähtitarhoihin, harmajan juosta
hölkytellessä omia aikojaan niemien ja lahtien poikki. Seppolaan
saavuttuaan virkkoi hän Eliinalle:

— Emme enää sure pikku Eliinan kuolemaa, minä löysin tähden,

jossa hän asuu.

Eliina naurahti. Jonni oli aivan kuin muuttunut, vaikka kasvot

näyttivätkin mielen riehujen rääkkäämiltä.

— Tulehan katsomaan.

Jonni tarttui Eliinan käsivarteen, he menivät yhdessä rapulle.

— Katsohan Otavan sarvesta oikeaan, tuo pieni ja kirkas tähti on

pikku
Eliinan uusi koti, sieltä hän näkee meidät.

— Hän näkee meidät, toisti Eliina. Olipa matkasi onnellinen.

— Minä piirrän pikku Eliinan kuvan, jotta mekin näemme hänet.

Jo seuraavana päivänä ryhtyi Jonni työhön. Hänellä oli vahva

taipumus piirtämiseen, liitukyniä ja piirustuspaperia oli hänellä
kouluajoilta. Häilyttyään monen vaiheilla, päätti hän piirustaa pikku
Eliinan kehdossa istuvana ja juuri sinä silmänräpäyksenä, kun tämä
on herännyt ja hieronut unen silmistään.

Piirroksen valmistuttua silmäili Jonni siihen tyytyväisesti. Hän oli

onnistunut luomaan kasvoihin jonkun piirteen, joka puhui ja eli ja
samalla muistutti johonkin määrin kuvan alkuperää, ainakin hänen ja
muiden seppolaisten mielestä. Puitteineen kuva sitte pantiin tuvan
seinään, jossa se, etäämmältä katsoen, teki onnistuneemman
vaikutuksen. Tyttö silmäili oveen päin tyhjämäisesti, kuten ainakin,
kun kaikki aistit eivät vielä olleet valveilla, toinen käsi piteli kehdon
laitaa, toinen, jolla oli unet hierottu, oli viety niskaan. Leuan alta oli
paidannapit auenneet, paljastaen toisen olkapään, jota hajallaan
olevat suortuvat tavoittelivat koskea —

Ankaraa tuisku- ja pakkastalvea seurasi lämmin kevät ja kesä.

Pääskysien rakennellessa pesiä syntyi Seppolaan poika, joka ristittiin
Toivoksi. Toinenkin tärkeä tapaus oli lähellä, nimittäin Martin ero.
Kolme vuotta oli saanut kuluneeksi umpeen, omintakeisen elämän
perustaminen, vuosia suunniteltu ja uneksittu, piti vihdoinkin
toteutua. Hosun kylän mailta vuokrasi Martti pikku talon, tulentekijä
oli valmiiksi silmitelty, Kaislassa kasvoi hänen varalleen hevonen,
joku lehmä ja lammaskin, löytyipä siellä muutakin pientä pötyä, joka
oli hänen nimellistään ja tervetullutta alkavan miehen talouteen.

Ennen Martin lähtöä maalattiin, Toivon syntymisen kunniaksi,

Seppolan kaikki rakennukset punaisiksi. Metsänhelmoissa sijaitseva
torppa sai siten iloisemman leiman, ja leiman vaikutusta lisäsi
taustassa seisova synkkä ja juhlallinen korpimetsä, joka monien
kilometrien laajuisena lähti levenemään katajikkomäen niskoilta
naapuripitäjän viljelysmaihin saakka.

Kaislan isäntä piti Martille häät, häiden jälestä seurasi muutto

Hosun kylän maille, pientä taloa viljelemään ja omatakeista elämää
alottamaan.

Noin Maltin askeleet olivat vieneet eroon Jonnista ja kaislalaisista.

RISTIINNAULITUN KUVA.

Martti jätti jälkeensä aukon, joka ei hevin täyttynyt. Jonni varsinkin

tunsi monesti itsensä avuttomaksi, tottunut kun oli kaikissa
tärkeimmissä töissä mukaantumaan renkinsä esityksiin. Martin
sijainen, Manu nimeltään, oli pehmytluonteinen, sitkeä työntekijä,
mutta henkisesti kokonaan alaikäinen sekä semmoisena opastettava
ja melkein kädestä ohjattava. Nuo ominaisuudet, vaikka vähemmän
hauskat, alkoivat Seppolan yksinäisyydessä vähä vähältä huvittaa
Jonnia, joka johdettavan asemasta nyt keikahti johtajan ja opastajan
asemaan. Tähän saakka oli kaikki työt tehty Martin vastuusen, mutta
tästä puoleen ne tehtiin isännän laskuun. Kävi työ näin tai noin, aina
oli Manu yhtä pehmeätuulinen, yhtä harras ja tyytyväinen, jotta
Jonnin toisinaan kävi oikein kateeksi miehen pehmeä luonne.

Naisapulainenkin heillä oli veres. Omavaltainen Naimi tuli

Seppolaan Eliinan avuksi, milloin häntä huvitti ja lähti taasen toviksi
kotiinsa, kun häntä niin huvitti, ja siitä sukeusi talouskomennon
koneistossa ratina, jota ei voitu vaiettaa muuten, kuin vakituisen
apulaisen hankkimisella. Kaislan emännän välityksellä onnistui valinta
hyvin. Tyttö, Silja, oli iloinen kuin västäräkki kynnöksellä, vaikka oli
kovia kokenut äitipuolen komennossa. Ja niin kirkassilmäinen, ettei
sille voinut syyn sattuessa edes harmistuakaan.
 — Silja, sanohan yksi asia, virkkoi Jonni, kun tyttö Eliinan kera
leipoi joululeipiä.

— Sanon kaksi ja kolmannen kaupanpäälliseksi.

— Oletko milloinkaan itkenyt?

— Minäkö itkenyt? Sepä kysymys.

— Niin, muistatko milloinkaan itkeneesi?

— Malttakaahan kun muistuttelen. Jo muistan. Itkin minä kerran.

— Mutta siitä lie enemmän kuin eilispäivä.

— Siitä on vuosia ainakin sen verran, kuin kädessäni on sormia.

— Ja minkä vuoksi silloin itkit?

— Vieras äiti sanoi minua rupisammakoksi. En tahtonut mielelläni

olla ruma. Menin isän polvien väliin ja intin, ettenhän ole
rupisammakon näköinen. Kun isä ei mitään vastannut, rupesin
itkemään. Se kerta oli ainoa ja olisinpa tahtonut silloin nähdä
suutani.

— Sitä minäkin olisin tahtonut nähdä.

Siljalla oli kaunis ääni, lauluja taisi hän paljo, varsinkin toisarvoisia
ja siitä alempia. Luonnon lapsena ei hän laulujensa laatua kyennyt
käsittämään, vaan lauloi yhtä hauskasti ja heleästi huonot kuin
hyvätkin. Pian kuitenkin asiat kääntyivät siksi, että Silja, ahkera
heläyttelijä, sai tirkistää arvottomien rekilaulujen maailmasta
ylemmille rinteille. Jonnin palatessa erään kerran kirkonkylästä oli
hänen reessään kansakoulun vanha harmooni, joka oli hylätty
nurkkaan uuden ja komeamman tieltä. Kone ei ollut korea
muodoltaan eikä ääneltään, mutta Seppolan tuvassa se menetteli
mainiosti. Jonnin mieleen juolahti, kansakoululla käydessään, että
tomuihinsa unhotettu kone jouti huvittamaan metsätorpan asujamia,
ja hän hankki sen rekeensä.

Alkoivat ankarat harjoitukset, tuottaen monta hupia sydäntalven

iltapuhteisiin. Tavoiteltiin laulaa neliäänisesti, Silja pantiin
sopraanoon, Eliina alttoon. Jonni lauloi ensi bassoa, Manu toista.
Viimemainittu lystit laati kovaoppisuudellaan. Toista bassoa
hangattiin kuin kiven kylkeä, väsyttiin väliin, alettiin uudelleen,
naurettiin ja harmistuttiin, mutta aina Manu »toimessa ja leikissä oli
yhtä totinen». Harjoituksien ja hankaamisien ensimmäinen hedelmä
oli »Honkain keskellä», jouluna kypsyi »Luostarikellot», jonka
romanttinen tunnelma viehätti laulajia suuresti.

Uuden vuoden vaiheilla tuli Naimi käymään Seppolaan. Lauluista ja

lauluharjoituksista ei virkattu sanaakaan. Vasta sinä iltana, jonka
huomenissa Naimin oli määrä liukua jälleen kotiinsa, virkkoi Jonni
aivan kuin sivumennen:

— Lauletaanpa laulu illan kunniaksi.

— Lauletaan, kannattivat Silja ja Eliina esitystä.

— Mikähän otettaisi?

Alkoi neljännestunnin kestävä valikoiminen. Joku oli vähemmän

kaunis, toista ei suosittu, kolmas oli mitätön rallatus j.n.e.

— Mutta lauletaanpa »Honkain keskellä», siinä on jotakin reipasta

ja kuitenkin aito suomalaista.
 — Lauletaan se.

Köörin jäsenet tulivat harmoonin lähelle; Jonni antoi äänet ja laulu

helähti raikkaana ilmoille. Toinen basso oli syöpynyt Manun veriin
eikä enää tippunut tielle.

Naimi oli kummissaan, seikka joka kyllä huomattiin. Lystiä aiottiin

jatkaa hänen kustannuksellaan. Kun oli pieni väliaika kulunut, kysyi
Jonni aivan vakavasti:

— Olisiko vielä laulaa toinenkin sävel?

— Mutta mikä? arveli Eliina.

Alkoi taasen kirjan selaileminen ja laulun etsiminen uusien

verukkeiden perusteella.

— Jos lauletaan »Luostari kellot», virkkoi Jonni vihdoinkin äkkiä,

kuten juolahduksen yllättämänä.

— Tosiaankin, lauletaanpa se,

Jonni otti taasen äänet ja antoi merkin. Romanttinen laulu loihti

hentoiset ilmeet Naimin kasvoille, silmäterät pyöristyivät ja laajenivat
kummastuksesta ihmettelyyn.

Toisen värssyn keskivaiheilla katsoi Eliina siskoonsa, pulahti

nauramaan, Jonni ja Silja lankesivat mukaan, ainoastaan Manu pysyi
jaloillaan, laulaen yksin äänensä värssyn loppuun saakka.

Se paljasti petoksen.

— Laulakaapa vielä kolmaskin laulu, pyysi Naimi, saatte viisi

penniä.
 — Ei me palkan eteen… kolmannen jälestä ruikuttaisit neljättä.

— Omiksi iloiksemme vain…

Päivien pehmetessä keväisemmiksi ja puhteitten lyhettyä laimeni

neliäänisen laulun into, lumien hävitessä se oli kokonaan syrjään
joutunut.

Sen vuoden kevät ja alkukesä oli omituinen. Oli sekaisin kuivaa ja

kosteata, kylmää ja lauhkeata, halla ja kato aivan kuin vaani joka
hetki viedäkseen viljat ja touot. Mutta kaikki säästyivät. Hallat olivat
maahalloja ja vaikka aamuisin monesti ruoho oli huurteinen ja vesi
jäätynyt pellonojan pohjissa, nyökkäili tähkä koskematonna, ja kun
Juhanina teki käänteen kesäisiin väreihin, huojuivat pellot satoa
täynnä, apilas levitti tuoksuaan ja touot kasvoivat kilvan apilaan
kera.

Sinä kesänä olivat Seppolan kaikki maat ensi kerran kasvussa.

Aitovarret ja valtaojaksimien nurmikot olivat sulautuneet sarkoihin,
kaikki savikot oli aura repinyt auki, kaikki lepikot olivat perkkautuneet
pelloiksi, ja siten viljeltävän maan pinta-ala oli kasvanut ainakin
kolmanneksen suuremmaksi entistä. Karjaakin oli kasvatettu. Eliinan
taitavan käden jäljet alkoivat tuntua talouskomennossa, riitti myydä
tuota ja tätä, joka aiheutti kaupunginmatkoja ja valutti hopeoita
isännän kukkaroon.

Se oli kaikki torpparin onnea, jo koulupoikana uneksittua.

Elettiin kesä, elettiin syksy, saavuttiin talven rajoille. Ja sairastui

Toivo. Heitti tänään syönnin, huomenna jäi makuulle, ylihuomenna jo
vaikeroi taudin käsissä.
 Tapaus kävi Jonnin voimien yli. Hän ei nukkunut eikä kyennyt
muuta ajattelemaan kuin kuolemaa. Pikku Eliinan viimeiset
silmänräpäykset ja heikot taistelut, joihin tuonen täytyi ryhtyä,
ennenkuin voitti saaliinsa, ne uudistuivat, hänen mieleensä joka
askeleella, ne olivat päivänä, iltana, yönä, ne olivat silmien mustana
merenä, josta ei voinut katsetta kääntää minnekkään muuanne. Kun
pojan poskiin nousivat punaiset kukat ja kun Jonni ajatteli, että ne
jäätyvät lumivalkeiksi ja että sairauden kaikkena loppuna on vain
pienen vartalon suoristus, silloin hänen päänsä tuli kuumaksi eikä
hän enää nähnyt eteensä.

Ja hän kaatui vuoteen omaksi ja rupesi hourailemaan.

Ensimmäisenä päivänä hoputti hän harmajata juoksemaan Toivon
hengen tähden, sitte hän puhui useimmiten pikku Eliinan tähdestä.
Viruttuaan jonkun päivän taudin käsissä, lähti Toivo toipumaan,
mutta Jonnin kanssa tuoni alkoi vakavammat leikit.

Tuli synkkä joulu Seppolaan. Nuori, elonvoimainen mies riuhtoilihe

tuonen kourissa, toisinaan hoputtaen harmajata juoksemaan,
toisinaan puhuen Eliinan tähdestä. Tähti tuikki kirkkaammin kuin
muut. Ja tähdessä asui pikku Eliina, isää odotellen ja viittaillen
luokseen. Pois verhot ikkunoista, pois pilvet taivaalta, että näkyy
pikku Eliinan tähti, ettei eksy maan asukas tähteen taivaltaessa.
Avaruus oli pimeä. Maailma oli pimeä. Kaikki oli pimeätä. Mutta pikku
Eliinan tähti loisti kirkkaasti. Loisti! Loisti!

Langat, jotka sairasta yhdistivät elämään, olivat enää tuiki heikot,

lääkärin saapuessa Seppolaan pitkän taipaleen takaa. Eliina kysyi
arasti:

— Onko enää toivoa?

 Lääkäri viivytteli vastausta.

— Elkää luottako minuun, luottakaa Jumalaan. Jos miehenne elää

viiden lyömään aamulla, jää hän eloon.

Kului ilta yöhön, yö aamupuoleen, kello löi kolme, löi neljä, mutta
yhä riuhtoili sairas.

— Eliinan tähti loistaa kirkkaasti. Loistaa! Loistaa! Avaruus on

pimeä.
Taivas on pimeä. Pois pilvet, pois pilven varjot, pois.

Kului puoli tuntia, sairaan hengitys helpponi, rinta rauhoittui, viittä

lyödessä painuivat silmäkannet umpeen ja sairas raukeni uneen.

— Miehenne jää eloon, virkkoi lääkäri Eliinalle. Minun apuni ei

auttanut, avun antoi Jumala. Menkää nyt nukkumaan.

Eliina meni tuvantakaiseen huoneeseen, jossa Toivo nukkui,

asettui polvilleen kehdon ääreen ja itki ja hymyili nukkuvalle
pojalleen.

Päivällä lähti lääkäri pois, annettuaan ohjeet, miten sairasta tuli

hoivata, ja pois lähtivät Eliinan omaisetkin ja Kaislan isäntä, mutta
Kaislan emäntä jäi Seppolaan muutamaksi päiväksi poikaansa
vaalimaan.

Toipuminen edistyi vitkaan. Ensi päivinä sairas enimmältään

nukkui, ollen hereillä vain moniaita minuutteja kerrallaan eikä
silloinkaan täysin tajuissa.

Viikon näin vierähdettyä seestyivät ajun voimat ensin ja erään

kerran valveuduttuaan kysyi sairas:
 — Elääkö Toivo?

— Elää.

— Sitte se olikin unta. Tuohan nähdäkseni.

Eliina riensi noutamaan Toivoa, mutta ennen hänen paluutaan ehti

Jonni jo nukkua.

Kului viikko, toinenkin, valveilla oloajat venyivät vähitellen

pitemmiksi, ajun voimat virkenivät nääntymystilastaan..

— Tunnen että kuolen.

— Elä ajattele sitä nyt, pyysi Eliina ja Kaislan emäntä, joka viivähti
yhä olemaan sairaan poikansa luona.

— Kuolema kauhistuttaa.

Ja se kauhistutti häntä. Toipumisen ensiaikoina ajatteli hän sitä

lyhyemmin ja satunnaisemmin, mutta ajun virketessä ja voimien
palatessa ryntäsi kuoleman tunne lujemmin ajatuksiin. Ja sen
rynnätessä tuli sen keralla kerran semmoinen silmänräpäys, jolloin
kuoleman takaa ammotti kauhistuttava tyhjyys, pimeys,
pohjattomuus. Teosoofiset mietelmät olivat olleet Jonnin lemmikkejä
nuorukaisvuosista saakka ja nyt, kuoleman tunteen ahdistaessa,
koetti hän turvautua entisiin lemmikkimietelmiinsä. Kuolema oli
niiden mukaan vain yksi kehityksen askel täydellisempää kohti,
alkuideaa kohti, johon sielu lopulta sulautuu monen inkarnatsioonin
kautta. Mutta mikähän inkarnatsiooni oli hänen ensimmäisensä? Joka
solmutta sulaisi jatkoksi hänen puuhilleen Seppolan viljelijänä ja
kunnallisien edistyspyrintöjen harrastajana. Kuoleman tunteen
ahdistaessa ei kysymys lainkaan tuntunut naurettavalta, päinvastoin.