SUPPOSITORIES
A suppository is a solid dosage form in which one or more APIs are dispersed
in a suitable base and molded or otherwise formed into a suitable shape for
insertion into the rectum to provide local or systemic effect.
Suppository is a solid dosage form intended for insertion into body
orifices where they melt, soften, or dissolve and produce local or
systemic therapeutic effects.
Uses And Applications
Examples of suppositories given for systemic results include diazepam,
metronidazole, progesterone, aminophylline, morphine, prochlorperazine,
chlorpromazine, thiethylperazine, indomethacin, diclofenac, ketoprofen,
naproxen, and ondansetron.
Advantages
● First-pass effect
● Drug stability
● Large dose drugs
● Irritating drugs
● Unpleasant tasting or smelling drugs
● In children, the rectal route is especially useful.
● In patients experiencing nausea and vomiting or when the patient is
unconscious
Disadvantages
● Lack of availability
● If suppositories are made on demand, they may be expensive
● Variable effectiveness
● Defecation may interrupt the absorption process of the drug
● The absorbing surface area of the rectum is much smaller than that of the
small intestine.
● The fluid content of the rectum is much less than that of the small
intestine, which may affect dissolution rate, etc.
● Degradation of some drugs by the microflora
Local Action
● Rectal suppositories intended for local action are most frequently used
to relieve
○ Constipation or
○ the pain, irritation, itching, and inflammation associated with
hemorrhoids or other anorectal conditions.
● Glycerin suppositories promote laxation by local irritation of the
mucous membranes.
● Vaginal suppositories or inserts intended for local effects are employed
mainly as
○ Contraceptives,
○ as antiseptics in feminine hygiene, and
○ as specific agents to combat an invading pathogen.
● Urethral suppositories may be antibacterial or a local anesthetic
preparative for a urethral examination
Systemic Action
● Suppositories for their systemic effects include
○ (a) prochlorperazine and chlorpromazine for the relief of nausea
and vomiting and as a tranquilizer;
○ (b) morphine and oxymorphone for opioid analgesia;
○ (c) ergotamine tartrate for the relief of migraine syndrome;
○ (d) indomethacin, a nonsteroidal anti-inflammatory analgesic and
antipyretic; and
○ (e) ondansetron for the relief of nausea and vomiting.
Some Factors of Drug Absorption From Rectal
Suppositories
Suppository Bases
play an important role in the release of the medication they hold and, therefore,
in the availability of the drug.
Requisites of Suppository bases
● Should be physically and chemically stable,
● Non Irritating, non toxic, non sensitizing,
● chemically and physiologically inert,
● compatible with a variety of drugs,
● stable during storage, and
● esthetically acceptable (free from objectionable odor and a pleasing
appearance).
● It should contract slightly on cooling to release itself from the mold with
requiring mold lubricants, has wetting and emulsifying properties, has a
high water number, and can be manufactured by molding by hand,
machine, compression, or extrusion.
● It should melt or dissolve in rectal fluids and should not bind or otherwise
interfere with the release or absorption of drug substances.
Classification of Bases
Fatty or Oleaginous Bases
● The most frequently employed suppository bases because of Cocoa
butter.
● Fatty or oleaginous materials used in suppository bases are
○ Cocoa butter (From Theobroma Oil, Triglyceride)
○ Fattibase (From Palm Kernel, Coconut Oil, Triglyceride)
○ Wecobee Bases (From Coconut Oil, Triglyceride)
○ Witepsol Bases (Triglycerides of Saturated F.As)
● Cocoa Butter
○ Fat obtained from the roasted seed of Theobroma cacao.
○ Chemically, it is a triglyceride primarily of oleopalmitostearin and
oleodistearin.
○ Melts at 30°C to 36°C. So, it is an ideal suppository base.
○ Because of its triglyceride content, cocoa butter exists in several
crystalline forms.
○ When cocoa butter is hastily or carelessly melted at a temperature
greatly exceeding the minimum required temperature and is then
quickly chilled, the result is alpha crystals with a melting point
much lower than that of the original cocoa butter.
○ That is why cocoa butter must be slowly and evenly melted.
○ If the formulation contains substances that may lower the MP of
Cocoa Butter (phenol, chloral hydrate) to the extent that the spst.
loses its solid form, some solidifying agents may also be added
within limits.
Water-Soluble and Water-Miscible Bases
The main members of this group are glycerinated gelatin and polyethylene
glycols.
Glycerinated Gelatin
○ Mostly used for vaginal local actions because it softens and slowly
with body fluids and hence provides slow release.
○ Because of glycerin, it is hygroscopic, and may absorb moisture
from atm. And lose its shape and consistency.
○ Hygroscopic nature also produces a dehydrating effect on body
tissues and causes irritation of mucosa. To avoid this, spst. May be
moistened with water prior to insertion.
Gelatin Glycerin Medicament
For Vaginal Spst. 20% 70% 10%
For Urethral spst. 60% 20% 20%
Polyethylene Glycols
○ These are polymers of ethylene oxide and water.
○ Most commonly used polyethylene glycols are PEG 300, 400, 600,
1,000, 1,500, 1,540, 3,350, 4,000, 6,000, and 8,000.
○ These numbers refer to molecular weight. Two or more PEGs can
be combined for desired consistency by fusion.
M. W. State
300-600 Clear, colorless liquids
600-1000 Semisolids
>1000 Wax Like white solids
○ They usually have MP considerably higher than body temp. Thus
provide slow release and good storage.
○ Since MP is higher, PEGs do not melt in the body but rather the
spst. slowly dissolves in the cavity as the fluid comes into contact.
○ Since spst. remain intact even in the body and only disintegrates
slowly upon fluid contact, chances of leaking from the orifice are
reduced.
○ Solid nature also prevents melting in fingertips while application.
○ The progesterone vaginal spst. Is the most commonly used PEG
based spst.
Formulation Variables
Physical State
Particle Size
Solubility
Viscosity
Brittleness
Volume Contraction
Drug Release Rates
Special Problems
Preparation of Suppository
Suppositories are prepared by two methods: (a) molding from a melt and (b)
hand rolling and shaping.
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, and
● (e) removing the formed suppositories from the mold.
Suppository Mold ()ﺳﺎﻧﭽﺎ
● Made from stainless steel, aluminum, brass, or plastic.
● Commercial molds can produce individual or large no. of spst.
● Those at community pharmacy produce 6-12 or more spst.
● Industrial molds can produce hundreds of spst. Per batch.
● The molds are opened for cleaning before and after preparation of a batch
of suppositories, closed when the melt is poured, and opened again to
remove the cold, molded suppositories.
● For easy removal of spst. from mold, it is generally lubricated.
(Lubrication is seldom necessary when the base contracts on cooling.)
● Each mold holds a specific volume and the Pharmacist should calibrate
each suppository mold for the usual base.
● Steps for calibration are
○ Make suppositories from a particular base alone.
○ To calculate weight of the mold, Weigh each spst.
○ Calculate total weight of all spst. + average weight of each spst.
○ To know the volume of the molds, Take one spst. and melt it in a
calibrated beaker. Note the volume occupied by the melt.
○ Repeat the process for all spst. and calculate the average vol.
occupied by one spst. + the total volume of all suppositories.
Determination of the Amount of Base Required
● The goal is to ensure the desired amount of medicament in every spst.
● Amount of required materials is calculated for additional one or two spst.
To compensate for losses.
First Method
● Because the volume of the mold is known, the volume of the drug
substances subtracted from the total volume of the mold will give the
volume of base required.
● In case of added substances having significant volume, the total volume
of these materials is subtracted from the volume of the mold, and the
appropriate amount of base is added.
● Because the bases are solid at room temperature, the volume of base may
be converted to weight from the density of the material.
● After adjusting for the preparation of an extra suppository or two, the
calculated amount is weighed.
Second Method
● Weigh the active ingredient for the preparation of a single suppository;
● Dissolve it or mix it with a portion of melted base insufficient to fill one
cavity of the mold and add the mixture to a cavity;
● Add additional melted base to the cavity to fill it completely;
● Allow the suppository to congeal and harden; and
● Remove the suppository from the mold and weigh it.
● The weight of the active ingredients subtracted from the weight of the
suppository yields the weight of the base.
● This amount of base multiplied by the number of suppositories to be
prepared in the mold is the total amount of base required.
Third Method
● Place all of the required medicaments for the preparation of the total
number of suppositories (including one extra) in a calibrated beaker,
● Add a portion of the melted base, and incorporate the drug substances.
● Then add sufficient melted base to reach the required volume of mixture
based on the original calibration of the volume of the mold.
Preparing and Pouring the Melt
● Using the least possible heat, the weighed suppository base material is
melted, generally over a water bath, because not a great deal of heat is
required.
● Usually, medicinal substances are incorporated into a portion of the
melted base by mixing on a glass or porcelain tile with a spatula.
● After incorporation, this material is stirred into the remaining base,
which has been allowed to cool almost to its congealing point.
● The melt is poured carefully and continuously into each cavity of the
mold
● If there are undissolved or suspended materials in the mixture which
have the tendency to settle, stir the mixture after each pouring.
● If the pouring is performed just above the congealing point and not when
the base is too fluid, the solid materials remain suspended.
● Alternatively, a small quantity of silica gel can be incorporated into the
formula to aid in keeping the active drug suspended.
● In filling each suppository cavity, the pouring must be continuous to
prevent l ayering
● 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 excessive material may form a continuous ribbon along the top of the
mold above the cavities. This use of extra suppository material prevents
formation of recessed dips in the ends of the suppositories
● The filled mold is usually placed in the refrigerator to hasten hardening.
● When the suppositories are hard, 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, with pressure being exerted principally on their ends and only
if needed on the tips.
● Generally, little or no pressure is required, and the suppositories simply
fall out of the mold when it is opened
Hand Rolling and Shaping
With ready availability of suppository molds of accommodating shapes and
sizes, there is little requirement for today’s pharmacist to shape suppositories by
hand. Hand rolling and shaping is a historic part o f the art of the pharmacist;
Preparation by Compression
● The suppository mass is placed in a cylinder; the cylinder is closed;
pressure is applied from one end, and the mass is forced out of the other
end into the mold or die.
● When the die is filled with the mass, a movable end plate at the back of
the die is removed, and when additional pressure is applied to the mass in
the cylinder, the formed suppositories are ejected. The end plate is
returned and the process is repeated until all of the mass has been used.
● In preparation for compression into the molds, the base and the other
formulative ingredients are combined by thorough mixing, the friction
of the process softening the base into a pastelike consistency.
● Heating the mortar in warm water (then drying it) greatly facilitates the
softening of the base and the mixing.
● Suited for substances that are heat labile or otherwise insoluble i n the
base.
● The disadvantage to compression is that the special suppository machine
is required and there is some limitation as to the shapes of suppositories
that can be made.
