Suppositories vs. Inserts vs.
Sticks Uses and Applications
SUPPOSITORIES
- Not very popular as a mode of administering
drugs but will probably always have a place in
medicine.
- a solid dosage form intended for insertion into
body orifices (e.g., rectum) where they melt,
soften, or dissolve and exert local or systemic
effects.
- shape and size of a suppository must be such
that it can be easily inserted into the intended
orifice without causing undue distension, and
once inserted, it must be retained for the
appropriate period.
- Inserted with the fingers but certain vaginal
inserts come with an applicator
Examples of suppositories
- Rectal suppositories: usually about 32 mm (1.5
inch) long, are cylindrical, and have one or both
ends tapered. Some are shaped like a bullet,
torpedo, or the little finger
o Examples: Bisacodyl (Dulcolax),
Hydrocortisone, Hydromorphone,
Indomethacin, Mesalamine,
Promethazine HCL
- Vaginal inserts – globular, oviform, or cone
shaped.
- Urethral inserts – also called bougies, usually
slender, pencil-shaped suppositories intended
for the insertion into the male or female
urethra.
Three reasons in using suppositories:
- Promote defecation
- Introduce drugs into the body
- Treat anorectal diseases
INSERTS
- a solid dosage form that is inserted into a
naturally occurring (nonsurgical) body cavity Local Action
other than the mouth or rectum, including the
vagina and urethra. - frequently used to relieve constipation or the
MEDICATION STICKS
- are a convenient form for administering topical
drugs. - Examples:
- it involves the history of cosmetics
- cylindrical in shape and range from 5-25 g
- Packaged in an applicator tube for topical
administration, can be adjusted to continually
expose new, fresh stick from inside the tube
- many active ingredients can be administered
rectally and achieve therapeutic blood levels
- Advantages of rectal administration:
First-pass effect: Avoiding, at least partially, the
first-pass effect that may result in higher blood
levels for those drugs subject to extensive first-
pass metabolism upon oral administration
Drug stability: Avoiding the breakdown of
certain drugs that are susceptible to gastric
degradation.
Large dose drugs: Ability to administer
somewhat larger doses of drugs than using oral
administration.
Irritating drugs: Ability to administer drugs that
may have an irritating effect on the oral or
gastrointestinal mucosa when administered
orally.
Unpleasant tasting or smelling drugs: Ability to
administer unpleasant tasting or smelling drugs
whose oral administration is limited.
In children, the rectal route is especially useful.
An ill child may refuse oral medication and may
fear injections
- Disadvantages:
Lack of flexibility leading to lack of availability,
may be expensive, exhibit variable
effectiveness, narrow therapeutic margin –
cannot be interchanged without risk of toxicity,
defection may interrupt absorption, absorbing
area of rectum is much smaller than small
intestine, fluid content in rectum is smaller than
small intestine affecting dissolution rate,
possibility of degradation due to microflora,
does of administration may be greater than oral.
pain, irritation, itching, and inflammation
associated with hemorrhoids or other anorectal
conditions.
o Antihemorrhoidal suppositories – local
anesthetics, vasoconstrictors,
astringents, analgesics, soothing
emollients, protective agents
o Glycerin suppositories - laxative…
… promote laxation through local irritation of the - Colonic Content: greater absorption may be
mucous membranes. expected from a rectum that is void than from
one that is distended with fecal matter.
o Vaginal suppositories – contraceptives,
antiseptics in feminine hygiene, combat Physicochemical Factors and Drug Effect
invading pathogen.
- Lipid–Water Solubility: A lipophilic drug that is
o Urethral suppositories – antibacterial or local
distributed in a fatty suppository base in low
anesthetic for urethral examination.
concentration has less tendency to escape to
o Sticks – local effect: hydration/ emollient,
the surrounding aqueous fluids than a
antibacterial, sunscreen, antipruritic, etc.
hydrophilic substance in a fatty base.
Systemic action - Particle size: the smaller the particle, the
greater the surface area, the more readily the
- the mucous membranes of the rectum and
dissolution of the particle, and the greater the
vagina permit the absorption of many soluble
chance for rapid absorption. It is preferable to
drugs.
avoid a too fine particle size because of the high
- Rectum is frequently used as site for systemic
increase of the viscosity of the melted excipient
absorption but not vagina
that can result from the use of excessively small
- Examples:
particles and possible difficulties in flow during
o Prochlorperazine and chlorpromazine
production.
– relief of nausea and vomiting,
tranquilizer
Suppository Bases
o Morphine and oxymorphone – opioid
- The first requisites for a suppository base is that
analgesia
it should remain solid at room temperature but
o Ergotamine tartrate – relief of migraine
soften, melt, or dissolve readily at body
syndrome
temperature.
o Indomethacin – nonsteroidal anti-
- Certain bases are more efficient in drug release
inflammatory analgesic and antipyretic
than others.
o Ondansetron – relief of nausea and
- Cocoa butter melts quickly at body temp but
vomiting
immiscible with body fluids. Fat-soluble drugs
Physiological Factors and Drug Effect seem to be released more readily from bases of
glycerinated gelatin or polyethylene glycol, both
- Circulation route: drugs absorbed rectally can of which dissolve slowly in body fluids.
bypass the portal circulation during their first
pass into the general circulation. Bypass the Nature of the base
liver thus exhibiting systemic effect.
- If the base interacts with the drug to inhibit its
- pH and lack of Buffering Capacity of the Rectal
release, drug absorption will be impaired or
fluids: pH of the rectal fluid is generally in the
even prevented. Also, if the base irritates the
range of 7.2 to 7.4, and it has negligible buffer
mucous membranes of the rectum, it may
capacity. Not generally be chemically changed
initiate a colonic response and prompt a bowel
by the rectal environment.
movement, eliminating the prospect of
o Rectal - it is generally accepted that at
complete drug release and absorption.
least 50% to 70% of the active
- the absence of any drug interaction between
ingredients administered rectally take
the medicinal agent and the suppository base,
the direct pathway, thus bypassing the
should be ascertained before or during
liver and avoiding the first-pass effect.
formulation.
o Vaginal - It is a highly elastic muscular
tube, located between the urethra and Classification of Bases
the rectum. The pH of the vagina is in
- two main categories and a third miscellaneous
the range of about 4 to 4.5.
group: (a) fatty or oleaginous bases, (b) water-
o Urethra
soluble or water-miscible bases, and (c)
miscellaneous bases, generally combinations of
lipophilic and hydrophilic substances.
 - should be physically and chemically stable,
nonirritating, nontoxic, non-sensitizing,
chemically and physiologically inert, compatible
Formulation variables
with a variety of drugs, stable during storage, and
esthetically acceptable.
Fatty or Oleaginous Bases
- most frequently employed suppository bases,
principally because of cocoa butter (fat obtained
from the roasted seed of Theobroma cacao)
- hydrogenated fatty acids of vegetable oils, such
as palm kernel oil and cottonseed oil.
- Glycerin containing compounds, palmitic and
stearic acids - glyceryl monostearate and glyceryl
monopalmitate
Physical State
- Fattibase, Wecobee bases, Witepsol bases
- Cocoa butter - ideal suppository base, melting
just below body temperature and yet
maintaining its solidity at usual room
temperatures but exhibits polymorphism
(crystalline forms). must be slowly and evenly
melted, preferably over a bath of warm water, to
avoid formation of the unstable crystalline form.
Water-Soluble and Water-Miscible Bases
- glycerinated gelatin and polyethylene glycols.
- Glycerinated gelatin base is most frequently
used in the preparation of vaginal suppositories,
prolonged local action is needed.
o Tend to absorb moisture (hygroscopic) -
must be protected from atmospheric
Particle size
moisture.
o may have a dehydrating effect and
irritate the tissues upon insertion. Water
minimizes this.
- Polyethylene glycol have been called on in
recent years to prepare progesterone vaginal
suppositories extemporaneously
o Used in premenstrual syndrome,
commonly molded with either a
polyethylene glycol base or a fatty acid
base.
o do not melt at body temperature but
rather dissolve slowly in the body’s fluids Solubility
- slower release of the medication from
the base.
o without danger of their softening
excessively in warm weather.
o their solid nature permits slow insertion
without fear that they will melt in the
fingertips unlike cocoa butter
o do not leak from the orifice, as do many
cocoa butter–based suppositories.
a. nature and form of the active principle (esters,
salts, complexes)
b. Physical State, particle dimensions, and the
specific surface of the product
c. Solubility of drug in various bases
d. Presence or absence of adjuvants added to the
active principle
e. The nature and type of dosage form in which the
active principle is incorporated
f. Pharmaceutical procedures
- For solids, the drug’s particle size may be very
important; the increase in surface area resulting
from decreased particle size can serve to
enhance its activity.
- For liquids, it is necessary to take up the liquid
into the suppository base using one of several
techniques such as forming an emulsion, adding
a drying powder, or adding a suitable thickening
agent when the liquid is mixed with the
suppository base
- For the semisolids or paste-type drugs, it can be
either mixed with a solid that will serve to thicken
the drug prior to mixing with the base or mixed
with the base to which a thickener is added.
- If a drug is readily soluble, the influence of
particle size may be minimal.
- For highly water-soluble drugs, the tendency will
be to dissolve and migrate to the rectal barrier.
- For poorly water-soluble drugs, the dissolution
rate will be slower, and a reduction in particle
size may increase the rate of dissolution by
exposing a greater surface area.
- This can also be affected by the nature of the
suppository base.
- Increased solubility of the active in the base can
improve product homogeneity but may delay the
release of the active if there is too great an
affinity of the drug for the suppository vehicle.
- If the active ingredient is insoluble in the base,
“suspension” or “emulsion”, it is necessary to
maintain homogeneity of the total mixture.
Viscosity
- If the viscosity of a base is low, it may be
necessary to add a suspending agent such as
silica gel to ensure that the drug is uniformly
dispersed until solidification occurs.
- the release rate of the drug may be slowed if the
viscosity of the base is very high.
Brittleness
- Brittle suppositories can be difficult to handle,
wrap, and use.
- In general, brittleness results when the
percentage of nonbase materials exceeds about
30%.
- Synthetic fat bases with high stearate
concentrations or those that are highly
hydrogenated are typically more brittle.
- Suppositories should not be placed in a freezer,
which also causes shock cooling and cracking.
Volume Contraction
- Bases, excipients, and active ingredients
generally occupy less space at lower
temperatures than at higher temperatures.
Molding
- During cooling process, the melt tends to
contract in size – allowing better release from
the mold but may form a cavity (undesirable)
Drug Release Rates
Special Problems
- Some active drugs require additional
preparation steps.
- Before vegetable extracts are added, they can
be moistened by levigation with a small amount
Lubrication of the Mold
of melted base.
- Hard, crystalline materials can be incorporated
either by pulverizing them to a fine state or by
dissolving them in a small quantity of solvent
- if the material is water soluble and an oily base
must be used, wool fat could be used.
- An aqueous solvent and a PEG base are
appropriate for water-soluble materials.
- If the base is oil miscible, one can add a few
drops of a bland oil like mineral oil.
- A number of ingredients are incompatible with
PEG bases, including benzocaine,
iodochlorhydroxyquin, sulfonamides,
ichthammol, aspirin, silver salts, and tannic acid.
- materials reported to have a tendency to
crystallize out of PEG include sodium barbital,
salicylic acid, and camphor.
- Suppositories prepared with PEG should not be
stored or dispensed in a polystyrene
prescription vial, as the polyethylene glycol will
adversely interact with polystyrene.
- All PEG suppositories should be dispensed in
glass or cardboard containers.
Preparation of Suppositories
a. Molding from a melt or
b. Hand rolling and shaping
- Melting the base -> incorporating any required
medicaments -> pouring melt into molds ->
allowing melt to cool and congeal into
suppositories -> removing the formed
suppositories from the mold
- Cocoa butter, glycerinated gelatin, polyethylene
glycol, and most other bases are suitable for
preparation by molding.
Suppository molds
- Individual plastic molds form a single
suppository
- Molds found in community pharmacy may form
6,12, or more suppositories
- Industrial molds form hundreds in a single batch
- Stainless steel, aluminum, brass, or plastic
- temporary molds may be successfully formed by
pressing heavy aluminum foil about an object
having the shape of the desired suppository,
then carefully removing the object and filling
the shaped foil with the melt.
- Lubrication is seldom necessary when the base
is cocoa butter or polyethylene glycol
- Lubrication (mineral oil) is usually necessary
with glycerinated gelatin.
Calibration of the mold
- 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 due to different
densities.
Manufacturing suppositories
- Calibration is needed
- 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).
Determination of the Amount of Base Required
- amount of drug should be provided in each
suppository
- (a)weigh the active ingredient for the
preparation of a single suppository; (b) dissolve
it or mix it (depending on its solubility in the
base) with a portion of melted base insufficient
to fill one cavity of the mold and add the mixture
to a cavity; (c) add additional melted base to the
cavity to fill it completely; (d) allow the
suppository to congeal and harden; and (e)
remove the suppository from the mold and
weigh it.
Preparation and Pouring the Melt
Quality control
- Using the least possible heat, the weighed
suppository base material is melted, generally
over a water bath.
- After incorporation of medicinal substances, this
material is stirred into the remaining base, which
has been allowed to cool almost to its congealing
point.
Packaging and Storage
- The melt is poured carefully and continuously
into each cavity of the mold, which has been
previously equilibrated to room temperature.
- To ensure a completely filled mold upon
congealing, the melt is poured excessively over
each opening, actually rising above the level of
the mold.
- the excess material is evenly scraped off of the
top of the mold with a spatula
- The filled mold is usually placed in the
refrigerator to hasten hardening.
- The mold is removed from the refrigerator and
allowed to come to room temperature. Then the
sections of the mold are separated, and the
suppositories are dislodged
Hand Rolling and Shaping
- ready availability of suppository molds of
accommodating shapes and sizes, there is little
requirement for today’s pharmacist to shape
suppositories by hand.
- suppositories are generally prepared by the melt
fusion method.
- The primary packaging of suppositories in the
automated process is comprised of five distinct
stages. The stages include forming, dosing,
cooling, sealing, and finishing
- The forming process determines the shape and
volume of the mold.
- the dosing station - the empty shells are aligned
with the nozzles of the dosing pump, and the
molten product is dosed into the empty shells.
- The cooling tunnels reduce temperature of the
molten mass in the shells. This allows the
product to solidify in the shells.
- sealing - the open top of the mold is closed. This
process is accomplished by reheating the top
edge of the film above the solidified suppository
- The finishing of the suppositories includes
perforating, notching, and cutting the molds into
the appropriate count strips.
- include identification, assay, and in some cases,
loss on drying, disintegration, and dissolution.
- stability considerations in dispensing practice for
suppositories include observation for excessive
softening and oil stains on packaging
- Glycerin suppositories and glycerinated gelatin
suppositories are packaged in tightly closed
glass containers to prevent a change in moisture
content.
- Suppositories prepared from a cocoa butter
base are usually individually wrapped or
otherwise separated in compartmented boxes
to prevent contact and adhesion.
- Suppositories containing light sensitive drugs
are individually wrapped in an opaque material
such as a metallic foil
- necessary to maintain them in a cool place.
- suppositories in high humidity may absorb
moisture and tend to become spongy,
- suppositories stored in places of extreme
dryness may lose moisture and become brittle
Microbiological stability
- suppository formulations do not contain
preservatives or antioxidants since water is
usually excluded.
- in the event water is present or the formulation
may support the growth of microorganisms, an
appropriate preservative may be indicated.
Beyond-Use Dating for compounded suppositories
- The completed compounded suppositories are
generally considered dry or nonaqueous and thus
provide a stable dosage form as long as they are
protected from moisture and heat.
- these preparations should have a beyond-use
date of 25% of the time remaining on the
expiration date if the compounded preparation is Vaginal Inserts
made using a manufactured product as the
source of the active drug, or 6 months, whichever
is earlier.
Expiration Dating for Manufactured Suppositories
- suppository must bear an expiration date
determined by appropriate stability testing.
- excessive softening is the major indication of
instability in suppositories, although some
suppositories may dry out and harden or shrivel.
- As a general rule (although there are exceptions),
suppositories should be stored in a refrigerator.
Informing and Educating the Patient
- the pharmacist is obligated to inform the patient
about the proper storage conditions (e.g., in a
cool, dry place—not in the bathroom)
- suggest a reasonable estimate of the time after
which the medication should be discarded
- When beyond-use dates are applied, the Vaginal Inserts (tablets)
pharmacist should emphasize to the patient that
the dates are applicable only when proper
storage conditions are observed.
Rectal Suppositories
- Suppositories are also intended to provide local
action within the perianal area.
- Local anesthetic suppositories are commonly
employed to relieve pruritus ani of various causes
and the pain sometimes associated with
hemorrhoids.
- Cathartic suppositories are contact-type agents
that act directly on the colonic mucosa to
produce normal peristalsis, more rapid acting
than orally administered medication.
- Pediatric suppositories are narrower and pencil
shaped than the typical bullet-shaped adult
suppository
Urethral Suppositories
- for urethral administration tend to be thinner
and tapered, often about 5 mm in diameter.
- treatment of local infections, and a much smaller
urethral suppository has been introduced for the
administration of alprostadil in the treatment of
erectile dysfunction
- These preparations are employed principally to
combat infections in the female genitourinary
tract, to restore the vaginal mucosa to its normal
state, and for contraception.
- The most commonly used base for vaginal inserts
consists of combinations of the various molecular
weight polyethylene glycols.
- Many vaginal inserts and other types of vaginal
dosage forms are buffered to an acid pH usually
about 4.5, consistent with the normal vagina -
discourages pathogenic organisms and provides
a favorable environment for eventual
recolonization by the acid-producing bacilli
normally found in the vagina
- The polyethylene glycol–based vaginal
suppositories are water miscible and are
generally sufficiently firm for the patient to
handle and insert without great difficulty.
- Vaginal inserts (tablets) are widely used today as
they are easy to manufacture, more stable, and
less messy.
- usually ovoid and are accompanied in their
packaging with a plastic inserter
- prepared by tablet compression - contain lactose
as the base or filler, a disintegrating agent such as
starch, a dispersing agent such as
polyvinylpyrrolidone, and a tablet lubricant such
as magnesium stearate.
- Some vaginal inserts are capsules of gelatin-
containing medication to be released
intravaginally.
 - Capsule insertion into the rectum can be - If the polyethylene glycol sup pository
facilitated by first lightly wet ting the capsule formulation does not contain at least 20% water,
with water. dipping it into water just prior to insertion
prevents moisture from being drawn from rectal
Medication Sticks
tissues
- many cosmetic preparations can serve as either - Bullet-shaped rectal suppositories should be
medications or drug vehicle bases. inserted point-end first.
- a fairly recent preparation, is used for both - one-half suppository, the patient should be told
cosmetic and medical purposes. Examples to cut the suppository in half lengthwise with a
include styptic pencils and lip balm sticks clean razor blade.
(Chapstick) -
- unique, convenient, relatively stable, easy-to-
prepare dosage form for the topical delivery of
drugs.
- Active drugs can include any agent that can be
applied directly to a specific skin site or over a
larger area of skin to relieve such discomforts as
muscle sprains and arthritis.
- glycerin, propylene glycol, alcohol, and
surfactants can increase the amount of
transdermal drug delivery.
- waxes, oils, or plain polymers such as PEGs alone
achieves a topical effect.
- Opaque bases include waxes, oils, PEGs, and the
like, whereas clear bases include sodium
stearate/glycerin mixtures.
- In general, the patient should be told to apply the
stick only to the involved area and not to the
surrounding skin.
- the patient should apply the medication liberally
over the area but only as needed.
- surface of the stick should be cleaned with a clean
tissue after each use, and, to avoid transmitting
infection, the product should not be shared with
others.

Clinical considerations

- Patients should be instructed on how to properly

store the suppository, unwrap a wrapped
suppository, and resolidify a melted suppository.
- If they must be stored in the refrigerator,
suppositories should be allowed to warm to room
temperature before insertion.
- The patient should be advised to rub cocoa butter
suppositories gently with the fingers to melt the
surface to provide lubrication for insertion.
- Glycerinated gelatin or polyethylene glycol
suppositories should be moistened with water to
enhance lubrication.