THERAPEUTICALLY SPEAKING

Suppositories:
TO HEPATIC CIRCULATION

an underutilized
dosage form TO GENERAL CIRCULATION
VLA. INFERIOR VENA CAVA

by JA Webster, R Dowse and RB Walker

" w i n ^
The rectal route is useful for the delivery of
both local acting and systemic drugs. ^ R
In certain cases suppositories are the best
Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)

form of therapy, or else they are an effective

alternative when oral therapy is not possible.
However; doctors rarely prescribe them and
patients are often reluctant to use them.
Figure 1: Schematic representation of the venous drainage of the
human rectum, with a suppository in position and showing the
superior rectal vein (1), the rectal mucosa (2), the middle rectal
vein (3), the inferior rectal vein (4) and the rectal cavity (5)

Is there
• Suppositories are medicated
Understanding how suppositories work, and
solid dosage forms, which are
their numerous uses, can overcome the
a difference
inserted into body orifices other
than the mouth.
aversion to this particular dosage form.
Pharmacists are in an ideal position to • The term suppository usually between oral and
educate doctors, other health care providers,
refers to the rectal dosage form.
Suppositories melt, soften or rectal absorption?
dissolve in the rectum where
and patients, on the benefits of using Absorption across the rectal
they exert a localized or
mucosa occurs in the same
suppositories and their correct use, and to systemic effect.
manner as in other parts of the
offer advice on any problems associated with gastrointestinal tract. However
• Suppositories vary in size and the dose of a drug administered
their use. shape. Those intended for adult rectally may need to be greater
use are generally about 2g in or less than the dose of the
size, and for paediatric use same drug given orally,
about 1g. because drug absorption from
the rectum is sometimes slower
• Suppositories are and more variable than with
About the authors conventionally bullet-shaped, other types of dosing. This may
JA Webster, BPharm; R Dowse PhD; and RB Walker PhD, School of torpedo-shaped or conical with be due to:
Pharmaceutical Sciences, Rhodes University, Grahamstown, South Africa. a rounded apex.

26 The Journal of MODERN PHARMACY / February 1996


• physiological factors
• the physicochemical nature of
the drug and suppository base
Physiological factors
The rectum is 15 to 20cm long
and has no villi, so there is a
relatively small surface area for
absorption. The rectum is
covered by only one to 3ml of
mucus and does not receive
any liquid through the intestinal
wall. This may hinder
dissolution of water-soluble
drugs. As the pH of the rectal
fluid is neutral and has little
buffering capacity, the ionic
form in which a drug is
absorbed will generally not be
changed. The presence of
faecal matter retards drug
absorption and may lead to
Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)
PHOLTEX - EFFECTIVE COUGH
Whenever persistent, dry hacking coughs are a problem, specially formulated P H O L T E X reduces !he frequency
and intensity of coughing, allowing easier breathing and restful sleep. P H O L T E X offers the silence of effective
relief for up to 1 0 h o u r s .
|52]RefNo. G8J I (jAcI 101/1965)
Eoch 10ml
expulsion of the suppository.
Enzymatic processes in the
rectum are reduced, thereby
minimizing possible enzymatic
degradation which occurs in
some drugs prior to absorption
in the gastrointestinal tract.
The site of drug absorption in
the rectum and subsequent
transport into the inferior,
middle or superior rectal veins
will determine whether a drug is
transported directly to the
general circulation, or via the
liver. The capillaries in the lower
and middle sections of the
rectum join to form the inferior
and middle rectal veins which
drain into the inferior vena
cava, and from there into the
general circulation. Any drug
absorbed in these regions will
^^^^^
bypass the liver.
Higher up in the rectum the
superior rectal vein drains into
the hepatic portal system.
Drugs which are absorbed in
this zone,will pass through the
liver and be metabolized by the
liver enzymes (Figure 1).
Although opinions differ, it is
thought that suppositories
generally remain in the lower to
middle section of the rectum,
and do not migrate higher into
the region of the superior rectal
vein. It has been suggested that
at least 50% of a rectal dose
can be assumed to avoid the
first-pass effect in this way.
Physicochemical
factors
The relative solubility of the
M i l l
P H O L T E X J U N I O R is also now available
^ ^ ^ ^ ^ for children from one to twelve years of
age, using a milder formulation.
PHOLTEX J U N I O R
[STjReg. No. 29/?0.1 1/0013
Eoch 5ml dose contains;
Pholcodine 5mg and
Methyl Hydroxybenzoote
as preservolive.
27 The Journal of
•Sc
THERAPEUTICALLY SPEAKING
drug in lipid and water as well
as the particle size of the drug
can affect absorption. Another
significant factor affecting
absorption is the type of
suppository base used, which
will regulate the partitioning of
the drug between the
suppository and the rectal
environment. The ability of the
base to melt, soften or dissolve
will also play a role in
determining the release
characteristics of the drug from
the base.
There are two basic types of
suppository bases:
Fatty bases, which melt at body
temperature, include
theobroma oil (cocoa butter)
and semi-synthetic mixtures of
mono-, di- and triglycerides,
I k l .
0,1% m/>
Pholtex
L O N G ACTING
C O U G H PREPARATION
3 M Innovation
3M Pharmaceuticals S.A. (Ply) Ud.
Co. Reg. No. 52/01640/07
181 Borbaro Rood, Elandslontein 1406
8osii O ' H o g o n a n d Assoc 7 1 5 7
MODERN PHARMACY / February 1996
 THERAPEUTICALLY SPEAKING

TABLE 1

D r u g s w h i c h a r e a v a i l a b l e in s u p p o s i t o r y f o r m

Trade name Drug Usage

Glycerine Suppositories Glycerine Constipation, evacuation ol bowel

Dulcolax; Capolax Bisacodyl

Posterisan Corpuscular elements, Metabolites of E coli Internal and external haemorrhage,

eczema, tears

Anugesic, Anusol Bismuth subgallate, Zinc oxide, Resorcinol Haemorrhoids, proctitis

Rectosan-A Hydrocortisone acetate, Bismuth subgallate
Anusol-HC Cinchocaine HCI, Hydrocortisone,
Framycetin, Aesculin
Proctosedyl Prednisolone, Clemizole undecylate,
Cinchocaine HCI
Scheriproct

Aminophyllin Aminophylline 500mg Bronchodilator for asthmatics and

Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)

chronic bronchitics. Poor, erratic

absorption — use not advised

Maxolon Metoclopramide 5mg, 10mg Nausea and vomiting — drug not lost
Valoid PS, Valoid AS Cyclizine 50mg, 100mg due to vomiting,as oral drug would be

Stemetil Prochlorperazine 5mg, 25mg Nausea and vomiting, migraine

Cafergot P-B Ergotamine tartrate, caffeine Migraine treatment, vascular headache

Arthrexin, Indocid Indomethacin 10Omg NSAIDs, alternatives to oral therapy,

Feldene, Xycam, Piroxrcam 20mg for relief of pain and inflammation of
Orucote Ketoprofen 100mg arthritis, gout, rheumatism and skeletal
Froben Flurbiprofen 100mg diseases. Often used at bedtime in
Naprosyn Naproxen 500mg place of the oral dose
Voltaren Diclofenac 12,5mg, 25mg

Ponstan Paediatric Mefenamic acid 125mg Analgesic/antipyretic for infants aged six
months to two years

Tramal Tramadol HCI 100mg Non-narcotic analgesic

Flagyl Metronidazole 500mg; 1g Anti-protozoal agent, used pre-opera-

tively and in post-operative situations
until oral medication is possible.

28 The Journal of MODERN PHARMACY / February 1996


such as Witepsol and
Suppocire.
W a t e r s o l u b l e and w a t e r
miscible bases, which dissolve
or disperse in rectal secretions
include glycerol-gelatine bases
and macrogols such as
polyethylene glycol (PEG).
PEG-based suppositories are
known to be irritant. To lessen
this irritation patients should be
advised to dip these
suppositories in water before
insertion. Other types of
suppository bases only
occasionally cause discomfort
— when they are used more
frequently than necessary or on
a long-term basis.
Why use
suppositories?
Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)
— when oral therapy
is not possible
If given a choice, most patients
would probably opt to take
tablets or other oral medication,
and shudder at the idea of
using a suppository. The oral
route is the most practical and
acceptable, as well as the most
economical means of
administering a drug. However,
oral medication is sometimes
contra-indicated, or it may not
be possible for a patient to take
solids or even liquids by mouth.
In this situation a suppository
could be the best treatment
option.
The rectal route is
convenient for administering
drugs to patients who are
unwilling or unable to swallow
medication, such as
unconscious patients; mentally
disturbed patients; infants and
children; patients who are
vomiting; patients with
pathological conditions of the
alimentary tract; and patients
recovering from surgery who
are unable to tolerate oral
therapy.
— to avoid
disadvantages
of oral medication
The use of suppositories rather
than oral medicine not only has
patient-orientated advantages,
but also has physiologic and
metabolic benefits.
• Drugs administered per
rectum are not inactivated by
enzymatic activity or the acidic
conditions in the stomach and
upper intestine.
• The first-pass' effect of the
liver enzymes may be partially
bypassed. This could be
advantageous to hepatic
patients, as it partly avoids drug
metabolism by the liver, and
subsequent possible damage to
the liver by drugs.
• Drugs known to irritate the
stomach, such as
aminophylline and non-steroidal
anti-inflammatory drugs
(NSAIDs), can be given in
suppository form without
causing gastric irritation. Acidic
NSAIDs irritate the gastric
mucosa in the following three
ways:
• The unionised, acidic drug
penetrates the mucosa, and as
it moves deeper into the tissue,
the pH rises and the drug
ionizes and lodges there,
forming a microcrystal. This
acidic crystal burns a hole in the
gastric mucosa, causing a
micropuncture, through which
blood leaks into the stomach.
This could become the site of
an ulcer.
• Prostaglandins (especially E
and I) increase mucin
production and decrease acid
production, thus protecting the
stomach. Since NSAIDs inhibit
prostaglandin synthesis, this
protection is lost.
• Prostaglandins E and I also
act as vasodilators. When their
synthesis is inhibited by
NSAIDs, the smaller gastric
vessels remain constricted.
Less blood and oxygen reach
the cells, which become
hypoxic and more susceptible
to damage.
The administration of
NSAIDs in suppository form will
avoid the first, local gastric-
irritant effect. The other two
effects are systemic and will
occur no matter how the NSAID
is administered.
— to exert a localized
effect on the rectum
The rectal route is not only used
as an alternative for drugs
exerting a systemic action.
Drugs exerting a localized effect
can also be incorporated into
suppository form.
Suppositories which have a
direct local action on the bowel
or rectum can be used instead
of oral purgatives. Glycerol and
bisacodyl are examples of
laxatives which exert their effect
by irritating the mucosa of the
rectum. The laxative does not
have to travel all the way down
the alimentary canal, but exerts
its effect locally at the desired
site of action.
Rectal suppositories are
often used to relieve the pain,
itching, irritation and
inflammation associated with
haemorrhoids and other rectal
conditions. They contain
combinations of local
anaesthetics, anti-inflammatory
agents, astringents, analgesics,
soothing emollients and
protective agents.
29 The Journal of M O D EPRHNA R M A C Y
THERAPEUTICALLY SPEAKING
How are
suppositories
used?
The convenience of this dosage
form should be weighed up
against the patient's aesthetic
objections to using
suppositories. No special
equipment or complicated
technique is needed. They are
easy to administer to wriggling
children — there is no need to
juggle measuring spoons or to
disguise medicine in pleasant
tasting food.
Most of us would probably
assume that the common-sense
way of inserting a suppository
would be pointed-end first.
However, if it has been inserted
this way the sphincter muscles
are unable to push the
suppository into the rectum,
which often leads to irritation
and even expulsion of the
suppository. On the other hand
if the blunt end of the
suppository is inserted first, the
suppository slips upward into
the rectum and is retained there.
Inserting a suppository may
be easier if the anus has been
lubricated. Glycerine, KY jelly or
petroleum jelly may be used
although these lubricants may
interfere with drug absorption.
What
is the role of the
pharmacist?
Pharmacists should keep in
mind the alternative of using
suppositories, particularly when
treating infants and children.
Patients and the parents of sick
children should be counselled
/ February 1996
 THERAPEUTICALLY SPEAKING

on the use of suppositories to antibiotics; or insulin the right form of the drug itself; drugs that can be formulated for
overcome their aversion to suppositories for diabetics. and possible modification of the rectal delivery will promote
them and to make sure that Most of the natural or synthetic formulation to include suppositories as a progressive
they know how to use them drugs can be formulated in absorption-promoting agents or dosage form.
properly. suppository form by careful adjuvants. (References are available on
The mother of a crying, selection of the correct base; Perhaps the wide scope of request from the authors)
feverish baby will probably
appreciate the option of an
analgesic-antipyretic
suppository, rather than
TAKE PHARMACY WEEK
struggling to get the sick child to
swallow a spoonful of medicine. PART March 11-16,1996
A patient who is unable to sleep IN...
at night because of arthritic pain contact JACKIE BURGER — PPAC telephone (011) 339-1682
might be advised to use an anti-
inflammatory suppository at
bedtime, instead of the oral

NOTICE BOARD
dose, which would cause
EfSISJEMaiSIS! 3MSJS!5I5iaiSIEI5J

I1
gastric irritation if taken on an
empty stomach.
Pharmacists may prescribe

I
laxative suppositories as well as
several of types that can be
Reproduced by Sabinet Gateway under licence granted by the Publisher ( dated 2012)

used to relieve haemorrhoids.

Y
They also have access to oung black urban/tes in p a „ »
aminophylline suppositories,
cyclizine and some of the non-
steroidal anti-inflammatories for
!1 I Merck (SA)Pty Ltd, a leaders
1 the supply of quality
pharmaceutolaodchern^
.
H w ^ S c S T 9 8
"

products, has been a w a r d ^ l S O

I
short term use in cases of acute

pain and inflammation. Most of
the other suppositories
mentioned require a doctor's
prescription, but pharmacists
teSx&^-J
9002 certification from the Soutn
i S n Bureau of Standards.
i Certification was ach.eved in
i I August 1995 for the Laboratoiy
PrSucts, Speciality Chemicals

IS
1
could suggest replacement of
and Pha^aceutteal divisions of
oral therapy with a suppository,
i Merck (SA). Merck (SA) is now
if the situation warrants it. / chemex 'QW . ^ ^
i one of only a select few
i p h a r m a c e u t i c a l c o m p a n i e s in
The future?
Suppositories have a wide i
I
1 1 South Africa to have
certification for the quaWy
I systems of its pharmaceutical
range of applications, and the
i business.
potential uses of the

1
suppository as a convenient

1
dosage form are expanding:
anti-malarial drugs; controlled-
release and slow-release
1 ^ssesofr^"l e C
1
suppositories; analgesic <h<>
suppositories that will allow
patients a pain-free sleep;
antibiotic suppositories for
children who refuse to swallow
II
medication or spit out costly

30 The Journal of MODERN PHARMACY / February 1996