Suppositories
Assist.lecturer
Qasim Allawi Bader
Definition
• Are conical or ovoid, solid prep. For insertion into
the body cavity where they melt,dissolve or
disperse and exert a local or a systemic effect.
• Their basis is fat,a wax or glycerol-gelatin gelly.
• They weight 1,2 or occasionally 4 g.
• In the past ,small suppositories known as cones
were prescribed for ear infection and long, very
narrow forms called bougies ,were used for nasal
and urethral infections.
Purposes of suppositories
• To exert a direct action on the rectum
especially to relieve the pain and irritation of
haemorrhoids and they contain:
 local anaesthetic e.g. benzocaine
Astringent e.g. Bismuth subgallate
Anti-inflammatory agents e.g. hydrocortisone
• To promot evacuation of the bowel e.g. laxatives.
• To provide a systemic effect which is of particular value for:
 Patients who are unconscious,mentally disturbed or who
cant administer drugs orally e.g. vomiting
 Adminstering drugs that cause gastric irritation e.g.
aminophylline
 Treating infants and children
 Drugs destroyed or inactivated by the pH or enzymatic
activity of the stomach or intestines need not be exposed
to these destructive environments.
 Drugs destroyed by portal circulation may bypass the liver
after rectal absorption (drugs enter the portal circulation
after oral administration and absorption).
Examples of drugs administered rectally in the form of
suppositories for their systemic effects include
(a) prochlorperazine and chlorpromazine for the relief
of nausea and vomiting and as a tranquilizer;
(b) oxymorphone HCl for opioid analgesia;
(c) ergotamine tartrate for the relief of migraine
syndrome;
(d) indomethacin, a nonsteroidal anti-inflamatory
analgesic and antipyretic; and
(e) ondansetron for the relief of nausea and vomiting.
SOME FACTORS OF DRUG ABSORPTION
FROM RECTAL SUPPOSITORIES
1. PHYSIOLOGIC FACTORS
 Colonic Content
• A drug will obviously have greater opportunity to make
contact with the absorbing surface of the rectum and colon
in an empty rectum. Therefore an evacuant enema may be
administered and allowed to act before the administration
of a suppository of a drug to be absorbed.
• Other conditions, such as diarrhea, colonic obstruction due
to tumorous growths, and tissue dehydration can all
influence the rate and degree of drug absorption from the
rectum.
 Circulation Route
• Drugs absorbed rectally, unlike those absorbed
after oral administration, bypass the portal
circulation during their first pass into the general
circulation, thereby enabling drugs otherwise
destroyed in the liver to exert systemic effects.
• The lower hemorrhoidal veins surrounding the
colon receive the absorbed drug and initiate its
circulation throughout the body, bypassing the
liver. Lymphatic circulation also assists in the
absorption of rectally administered drugs.
pH and Lack of Buffering Capacity of the
Rectal Fluids
• Because rectal fluids are essentially neutral in pH and
have no effective buffer capacity, the form in which the
drug is administered will not generally be chemically
changed by the environment.
• The suppository base has a marked influence on the
release of active constituents. While cocoa butter
melts rapidly at body temperature, because of its
immiscibility with fluids, it fails to release fat-soluble
drugs readily.
• .
• For systemic drug action using a cocoa butter
base, it is preferable to incorporate the ionized
(salt) form rather than the un-ionized (base)
form of a drug to maximize bioavailability.
Although un- ionized drugs more readily
partition out of water-miscible bases such as
glycerinated gelatin and polyethylene glycol,
the bases themselves tend to dissolve slowly
and thus retard release of the drug
2. PHYSICOCHEMICAL FACTORS OF THE DRUG AND
SUPPOSITORY BASE
 Lipid–Water Solubility
• The lipid–water partition coefficient of a drug is an
important consideration in the selection of the
suppository base and in anticipating drug release
from that base.
• A lipophilic drug that is distributed in a fatty
suppository base in low concentration has less
tendency to escape to the surrounding aqueous
fluids than a hydrophilic substance in a fatty base.
• Water soluble bases—for example, polyethylene
glycols—that dissolve in the anorectal fluids
release for absorption water-soluble and oilsoluble drugs.
• Naturally, the more drug a base contains, the
more drug will be available for absorption.
• However, if the concentration of a drug in the
intestinal lumen is above a particular amount,
which varies with the drug, the rate of absorption
is not changed by a further increase in the
concentration of the drug
Particle Size
• For undissolved drugs in a suppository, the
size of the drug particle will influence its rate
of dissolution and its availability for
absorption.
• The smaller the particle, the greater the
surface area, the more readily the dissolution
of the particle and the greater the chance for
rapid absorption.
Nature of the Base
• The base must be capable of melting, softening,
or dissolving to release its drug for absorption. If
the base interacts with the drug to inhibit its
release, drug absorption will be impaired or even
prevented. Also, if the base irritates the mucous
membranes of the rectum, it may initiate a
colonic response and prompt a bowel movement,
eliminating the prospect of complete drug
release and absorption.
• In a study of the bioavailability of aspirin from five brands
of commercial suppositories product, only about 40% of
the dose was absorbed when the retention time in the
bowel was limited to 2 hours. Thus, the absorption rates
were considered exceedingly low, especially when
compared with orally administered aspirin.
• Because of the possibility of chemical and/or physical
interactions between the medicinal agent and the
suppository base, which may affect the stability and/or
bioavailability of the drug, the absence of any drug
interaction between the two agents should be ascertained
before or during formulation.
Properties of an ideal suppository base
1. Should be melt at body temp.or dissolved or dispersed in
body fluids.
2. Release any medication readily.
3. Keep its shape during handling.
4. Non toxic and non irritant to the mucous membrane.
5. Stable on storage.
6. Compatible with any added medication
7. Stable when heated above its melting point
8. Easily moulded and not adhere to the mould.
9. Mouldable by pouring or cold compression.
Types of suppository bases
 Fatty or oleaginous bases,
 Water-soluble or water-miscible bases,and
 Miscellaneous bases, generally combinations
of lipophilic and hydrophilic substances
Fatty or Oleaginous Bases
• Theobroma oil (cocoa butter)
Advantages
• Has a melting point range of 30-36 °C.
• Readily liquefy on warming and rapid setting
on cooling.
• Miscible with many ingredient.
• Blandness, which is a valuable feature when
suppository is intended to allay irritation
Disadvantages
 Polymorphism:
• When melted and cooled it solidifies in different
crystalline forms, depending on the temp. of the
melting, rate of the cooling and size of the mass.
• If melted at not more than 36 °C and slowly cooled it
will form stable beta form with normal melting point.
• If overheated it may produce, on cooling unstable
gamma crystal which melt at 15 °C ,or alpha crystals,
melting at 20 °C.
• This lowering in solidification point lead to
sedimentation of suspended solids.
Adherence to the mould
Because theobroma oil doesn’t contract enough
on cooling to loosen the supp. In the mould,
sticking may occur .this is preventing by
lubricating the mould before use.
 Softening point too low for hot climate
To rise the softening point ,white bees wax may
be added to theobroma oil supp. Intended for
use in tropical and subtropical countries.
 melting point reduced by soluble ing.
• Substances such as chloral hydrate ,that dissolve in
theobroma oil , may lower its melting point to such extent
that the supp. Is too soft for use .
 slow deterioration during storage
This is due to oxidation of unsaturated glycerides.
 poor water absorbing capacity
This fault can be improved by the addition of
emulsifying agent .
 leakage from the body
Relatively high cost.
• Synthetic fats
It is used as substitute free from disadvantages
of theobroma oil .
It was produced by hydrolyzing the vegetable oil
then hydrogenating the free fatty acids and
finally re-esterifying the acids by heating with
glycerol.
• They are superior to theobroma oil because
1. Their solidifying points are unaffected by overheating.
2. Have good resistance to oxidation
3. Small difference bet. Melting and setting points (1.5-2)hence
i. They set quickly
ii. The risk of sedimentation is low
iii. Easier to administer. When the setting point of a base is well
below the melting point, the supp. Soften quickly when
handled and become too slippery to administer.
4. Its availability in a series of grades with slightly
difference in M.P. ranges and degree of hardness.
5. Has good water absorbing capacity because they
usually contain a proportion of glycerides some of
which are w/o E.A.
6. They contact significantly on cooling
7. They produce supp. That is white and almost
odoureless and has very attractive, clean and
polished appearance .
• Disadvantages of synthetic fatty bases
1. They become brittle if cooled quickly, 0.05 %
of polysorbate 80 help to correct this fault.
2. They are more fluid than theobroma oil when
melted and at this stage sedimentation may
occur. Thickinners such as Mg stearate
,bentonite and colloidal silicon dioxide may
be added to reduce this.
Water-Soluble and Water-Miscible
Bases
1. Glycero-gelatin
• Is a mix. Of glycerol and water made into stiff jelly by adding
gelatin.
• Contain about 14% w/w gelatin( 18% in hot climates) and
70% w/w glycerol .
• Glycero-gelatin dissolves in body secretions and therefore is
preferable over the fatty base for administering antiseptics.
• Since solution is slow,drug release is more prolonged than
from fatty bases.
• At present the B.P allows a maximum disintegration time of 1
hr for glycerol supp.
• Glycero-gelatin bases are less often used than fatty bases
because:
1. They have a physiological action (laxatives)
2. More difficult to prepare and handled.
3. Their solution time depends on the content and quality of the
gelatin and the age of the base
4. They are hygroscopic leading to dehydration of the rectal
mucosa.
5. Gelatin is incompatible with protein precipitant like tannic
acid.
• Tow types of gelatin found :
1. Type A , made by acid hydrolysis, isoelectric
point between 7 and 9 on the acid side of this
range behaves as cationic agent most effective
at about pH 3.2
2. Type B, made by liming, isoelectric point
between 4 and 5 on the alkaline side of this
range behaves as anionic agent ,most effective
at pH 7-8
Cationic and anionic antibacterial agents should not
be formulated with gelatin of opposite charge.
Macrogols
• Are a mixture of polycondensation products of
ethylene oxide and water and they are
described by numbers representing their
average molecular weight. They vary in
consistency from viscous liq. To waxy solids
Macrogols 200-400
viscous liq.
1500
greasy ,semisolid
1540-6000
waxy solids
• Avantages :
1. They used in mixture of grades has a M.P. above
42 °C so, cool storage is not req.and they are
satisfactory for use in hot climates
2. They are gradually dissolved and dispersed
freeing their medication slowly providing longer
action than fatty bases
3. Their physical properties can be varied by
suitable admixture of high and low polymer
High polymers give hard products that disintegrate
and release their drugs slowly.
5. Don’t stick to the mould so, no lubricant is
req.
6. No leakage from the body due to the high
viscosity of their solution after melt.
7. Have good water absorbing capacity
8. Have clean smooth appearance.
• Disadvantages
1. They are hygroscopic
2. Retention of the drug in the liquefied base in the
body (bec. Of its good solvent properties ) with
conseq.reduction in therapeutic activity
3. Products sometimes fracture on storage, particularely
if they contain water bec. Of high solubility of
macrogols which can lead to supersaturated solution
in the water and subsequent crystallization. Leading
to brittleness.
4. Crystall growth.which in addition to making the
product brittle , the crystals may be irritating and take
longer time to dissolve.
5. They are incompatible with bismuth salts,tannins and
phenols leading to liquification of the supp.
Miscellaneous Bases
• In the miscellaneous group of bases are mixtures of
oleaginous and water-soluble or water- miscible
materials. These materials may be chemical or physical
mixtures. Some are preformed emulsions, generally of
the water-in-oil type, or they may be capable of
dispersing in aqueous fluids.
• Mixtures of many fatty bases (including cocoa butter)
with emulsifying agents capable of forming water-in-oil
emulsions have been prepared. These bases hold water
or aqueous solutions and are said to be hydrophilic.
PREPARATION
OF SUPPOSITORIES
• Suppositories are prepared by three methods:
1. Molding from a melt,
2. Compression, and
3. Hand rolling and shaping.
The method most frequently employed both on
a small scale and on an industrial scale is
molding.
PREPARATION BY MOLDING
• The steps in molding include
(a) melting the base,
(b) incorporating any required medicaments,
(c) pouring the melt into molds,
(d) allowing the melt to cool and congeal into suppositories,
(e) removing the formed suppositories from the mold.
• Cocoa butter, glycerinated gelatin, polyethylene glycol,
and most other bases are suitable for preparation by
molding.
• Calibration of the Mold
Each individual mold is capable of holding a specific
volume of material in each of its openings.
Because of the difference in the densities of the
materials, if the base is cocoa butter, the weight of the
suppositories will differ from the weight of suppositories
prepared in the same mold with a base of polyethylene
glycols. Similarly, any added medicinal agent alters the
density of the base, and the weight of the resulting
suppository differs from that of those prepared with base
material alone.
• The first step in calibration of a mold is to
prepare molded suppositories from base
material alone. After removal from the mold,
the suppositories are weighed and the total
weight and average weight of each
suppository are recorded (for the particular
base used).