Chapter 12 – Suppositories

Local Actions:
Suppositories Once inserted, the suppository base melts, softens or dissolves, distributing
 Derived from the Latin term supponere, meaning “to place the medicaments it carries to the tissues of the region.
under”. Rectal Suppositories: relieves constipation or pain irritation, itching and
 SUB – under ; PONERE – to place inflammation associated with hemorrhoids or other anorectal conditions
(pinworms, dermatitis)
 Are solid dosage forms intended for insertion into body orifices
Vaginal suppositories: as antiseptic in feminine hygiene and as specific agents
where they melt, soften, or dissolved and exert localized or
to combat an invading pathogen. (vaginitis - by Trichomonas vaginalis and
systemic effects.
Candida albicans)
Suppositories Shape Dimensions Urethral Suppositories: as antibacterial and as a local anesthetic preparatory
to urethral examination
1.Rectal Long, cylindrical and have Infant: 1 gram
Suppository one or both ends tapered. Adult: 2 grams Systemic Actions:
For system effects, the mucous membranes of the rectum and vagina
2.Vaginal Globular, oviform, or conical About 3 to 5 permits absorption of many soluble drugs.
Suppository shaped. grams Rectal suppositories:
“Pessaries” Aminophylline & Theophylline - relief of asthma
Prochlorperazine & Chlorpromazine - nausea & vomiting, & as
3. Urethral Slender, pencil-shaped For males: 4 g,
tranquilizer
Suppositories suppositories. 100-150 mm long.
Chloral hydrate -sedative and hypnotic
“Bougies” Females: 2 g, 60
Oxymorphine HCl - narcotic analgesic
to 70 mm.
Belladonna & Opium - analgesia and antispasmodic effect
Ergotamine tartrate - migraine syndrome
Types of Suppositories Aspirin - analgesic and antipyretic
1. Rectally
2. Occasionally Urethrally Factors Affecting Drug Absorption of Suppositories
3. Nasal Insertion Physiological Factors:
4. Vaginally 1. Colonic content - When systemic effects are desired from the
5. Rarely aurally administration of a medicated suppository, greater absorption
may be expected from a rectum that is empty than one that is
distended w/ fecal matter because of more absorbing surface.
So when deemed desirable, an evacuate enema will be used first.
Characteristics based on Administration Other conditions: diarrhea, colonic obstruction due to tumors,
1. They have various weights and shapes, the shapes and size of a tissue dehydration can influence the rate and degree of
suppository must be such that it is capable of being easily inserted absorption
without causing any distension and once inserted must be 2. Circulation Route - drugs absorbed rectally, unlike those absorbed
retained for the appropriate period of time. orally, by pass the portal circulation during their first pass into the
2. Rectal Suppository are usually 32 mm (1 1/2 inches) in length, are general circulation, thereby enabling drugs otherwise destroyed
cylindrical, have one or both ends tapered. in the liver to exert systemic effect.
3. The USP and NF states that the adult Rectal suppositories weigh The lower hemorrhoidal veins surrounding the colon receive the
about 2 grams when cocoa butter (theobroma oil), as vehicle, is absorbed drug and initiate its circulation throughout the body, by
employed as based. passing the liver.
3. pH and Lack of Buffering Capacity of the Rectal Glands
Nasal Suppositories - “Burginarium” The rectal fluids are essentially neutral in pH and have no
- with a glycerinated gelatin base. effective buffer capacity so no chemical change will occur in this
area.
Aural Suppositories (“Ear Cones”) The suppository base has a marked influence in the release of
- pencil-shaped suppositories similar in shape to urethral active constituents incorporated into it.
suppositories but shorter in length, generally about 32 mm Cocoa butter melts rapidly at body temperature but immiscible
long. with body fluids and therefore fails to readily release fat-soluble
- have been prepared with cocoa butter base drugs.
For systemic drug action, it is preferable to incorporate the
Advantages: ionized rather than the unionized form of a drug to maximize
1. When a drug cannot be tolerated, cause to vomit orally bioavailability
2. When a drugs cannot be swallowed - causing choking 4. Physiochemical Factors:
3. When a drug may be decomposed or inactivated by the pH or a. Drug
enzymes in the GIT i. Relative solubility of the drug in lipid & in water
4. Rectal suppositories administered for its systemic effects but ii. Particle size of a dispersed drug
containing drugs destroyed in the liver are better than oral 1) Lipid-water solubility - a lipophilic drug that
administration since rectal administration, liver is by passed. is distributed in a fatty suppository base in
Disadvantage - Inconvenient absorption is irregular and difficult to predict
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 low concentration has loss of a tendency to
escape to the surrounding aqueous fluids
than would a hydrophilic substance present
in fatty base to an extent approaching the
saturation.
Ex.: polyethylene glycols - which dissolve in
the anorectal fluids, release for absorption
both water-soluble and oil-soluble drugs.
2) Particle size - For drugs present in the
suppository in the undissolved state, the
size of the particle will influence the
amount release and dissolved in absorption.
“The smaller the particle size, the more
readily the dissolution of the particle and
the greater the chance for rapid absorption”
b. Suppository base
i. Ability to melt, soften or dissolve at body temperature
ii. Ability to release the drug substance
iii. It is hydrophilic or hydrophobic character
1) Nature of the base: must be capable of
melting, softening, or dissolving to release
its drug components for absorption.
2) Undesirable Characteristics Of A Base
a) That which interact with the
drug inhibiting its release such
that the drug absorption will be
prevented or delayed.
b) That which is irritating to the
mucous membranes of the
rectum thus initiating a colonic
response and prompt a bowel
movement, negating the
prospect of thorough drug
release and absorption.
Classification Of Suppository Bases
1. Fatty or Oleaginous bases
a. When a base is not specified, Cocoa Butter is used
b. Other oleaginous materials:
i. Hydrogenated fatty acids of vegetable oils - palm,
kernel oil, and cotton seed oil
ii. Fat bases compounds - glycerin with the higher
molecular weight fatty acids: palmitic and stearic
acids
iii. Example of Suppositories with Cocoa Butter as a
Base
1) Cotmar
2) Dehydag
3) Wecobee
4) Witepsol
5) Fattybase
2. Water-soluble or water-miscible bases
a. The main members of this group are based of
i. Glycerinated gelatin
- USP Preparation Of Glycerinated Gelatin
1) Weigh medicinal substance
2) Add water to make 10 grams
3) Dissolved or mix 20 mL of glycerin and
20 g of granular gelatin.
4) Heat on a steam bath until all gelatin
dissolved
5) Pour the melted mixture into molds &
allow to congeal.
ii. Bases of polyethylene glycols
Polyethylene Glycol
1) polymers of ethylene oxide and water,
prepared to various chain lengths,
molecular weights, and physical
states. They are available in a number
of molecular weights ranges 200, 400,
600, 1000, 1500, 1540, 3350, 4000,
6000 & 8000.
2) Polyethylene glycols with average MW
of 200, 400, and 600 are clear,
colorless liquids. Those greater than
1000 are wax like, white solids with
hardness increasing with an increase
in molecular weight.
Ex.: Polybase
***Glycerinated gelatin based suppositories have
tendencies to absorb moisture due to the hygroscopic
nature of glycerin causing the following effect:
Ex.: Jell-O
- May lose their shape and consistency
- May lose dehydrating effect and be irritating to the tissues upon
insertion
3. Miscellaneous bases, (combination of lipophilic and hydrophilic)
a. Mixture of oleaginous and water-soluble materials
Ex.: Polyoxyl 40 stearate (mixture of monostearate &
distearate esters of mixed polyethylene diols & the
free glycols)
b. Mixtures of many fatty acids (including Cocoa Butter)
with emulsifying agents capable of forming W/O
emulsion. Also referred to as “hydrophilic” suppository
base.
c. A soap as a base like glycerin suppositories which have
sodium stearate; a soap as the base are included.
Preparations Of Suppositories
1. Molding from a melt/Fusion (Pour Molding)
2. Cold Compression (No heat Application)
3. Hand molding/rolling and shaping (No Heat Application)
4. Compression in a tablet press
*** The method most commonly employed in both small scale and industrial
scale is molding.
Preparation By Molding
1. Melting of the base preferably in water or steam bath to avoid
local overheating.
2. Incorporating the required medicament - either emulsified or
suspend in it.
3. Pouring the melt into cooled metal molds, which are usually
chrome or nickel plate.
4. Allowing the melt to cool and congeal thoroughly using
refrigerator in a small scale or refrigerated air on a larger scale.
5. Removing the formed suppositories from the mold.
Note: Suppositories of cocoa butter, glycerinated gelatin, polyethylene
glycol and most other suppository bases are suitable for preparation by
molding.
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Suppository Molds Density factor: 1.1
- Molds in common use are made from stainless steel, aluminum, Dosage: 0.5000 gram/suppository
plastic. The molds which separate into sections generally Suppository base: Cocoa butter
longitudinally, are opened for cleaning before and after preparing Blank weight of suppository: 2.000 grams
a batch of suppository, closed when the melt is poured and Calculations:
opened again to removed the cold, molded suppository.
0.5000/1.1 = 0.4545 g weight of cocoa butter which should be
Scratches in the molds should be avoided especially the plastic.
replaced by 0.5 g of the drug

Lubrication Of The Molds 2.000 g - 0.4545 = 1.5455 g weight of cocoa butter required by
- Depending upon the formulation, suppository molds may require the suppository
lubrication before the melt is poured to facilitate the clean and
easy removal of the molded suppository. 0.5000 + 1.5455 = 2.0455 g actual weight of suppository
- Lubricant is a thin coating of mineral oil or expressed almond oil
applied with the finger to the molding surface is sufficient. 2. Second Method
o Requires the following steps:
Calibration Of The Molds a. Weigh the active ingredient for the preparation
 It is important the pharmacist calibrate each of his of a single suppository
suppository molds for the suppository bases that b. Dissolve or mix it with a portion of melted base
he generally employs to have proper quantity of insufficient to fill one cavity of the mold.
medicaments. c. Place the mixture to the mold
a. The suppositories are weighed and the total weight & d. Add additional melted base to the cavity to
average weight of each suppository are recorded. completely fill the mold.
b. To determine the volume of the mold, the e. Remove the suppository from mold and weigh
suppositories are carefully melted in a calibrated f. Then subtract the weight of the ingredient from
beaker. the total weight of the suppository to get the
c. The volume of the melt is determine for the total amount of the base needed.
number as well as the average of one suppository. g. Then multiplied by the number of suppository
made to get the total base needed.
Suppository Molds and Packaging Preparation of ingredient:
1. Aluminum metal molds  Glycerin
 come in a variety of cavity sizes and with a variety of  Stearic acid
number of cavities per mold  Sodium carbonate
 Common sizes vary from 1 g to 2.5 g, and common number  Water
of cavities range from 6 cavities up to 100 cavities 3. Preparing the mold
 The two halves of the mold are held together with either 4. Base preparation
nuts or some molds have 1 centered screw. 5. Mxing and pouring
2. Plastic suppository shells Opening a suppository mold
 come in long strips that can be torn into any number of  The suppository mixture is poured into the cavities of a
cavities closed mold. When the suppository mixture has
 These disposable molds do not need any lubrication congealed, the excess mass is removed from the top
regardless of the suppository mixture surface of the mold & the mold is separated into the
 available in 1 g to 5 g sizes, and many different colors. two halves.
 Advantage: if the suppository should melt, it will not run out  An efficient way to separate the mold is to remove the
of the mold. If the material can congeals again, it will retain wing nuts or loosen the centered screw and place the
the suppository shape. mold so that the posts rest on the table top.
3. Flexible rubber molds  Then, apply a downward pressure only on the bottom
 can be packaged with the suppository still in the mold. half of the mold.
Generally the mold is placed in a special box.  A knife or spatula should not be used to pry the two
halves apart. This will damage the matching mold faces
Determination Of The Amount Of Base Required which have been accurately machined to give a tight
1. First Method seal.
o Subtract the volume of the drug substance from the  Suppository shells can be opened by peeling apart the
total volume needed. two tabs at the bottom of the shell.
For example: If 12 mL of Cocoa butter are required to 6. Cooling and Finishing
fill a suppository mold and if the medicaments in the 7. Packaging
formula have a collection volume of 2.8 mL the 9.2 mL
of Cocoa butter will be required. By mutiplying 9.2 mL Suppository packaging
times the density of cocoa butter, 0.86 g/mL the Strip ware
weight result is 7.9 g will required  Strips (bars) with 10, 12, 20 or 24 individual cells
Another example: For Cocoa butter suppositories  with or without punching
Active ingredient: Aminophylline  one side target printing
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  white or transparency or one side white and one side 3. A broad bladed spatula or flat board is used to roll it into a
transparency foil cylinder on a pile tile.
 various opening methods like tear open slot, tear open strap, peel 4. Cut with a spatula into sections and shaped as desired.
off strap, “short”
Roll ware Compression In A Tablet Press
 with or without perforation between the cells 1. Carbon dioxide - releasing tablet - made up of dried sodium
 one or two side target printing biphosphate, sodium bicarbonate and starch. This compressed
 white or transparency or one side white and one side rectal suppository is dipped or sprayed with a coating of water
transparency foil soluble polyethylene glycol to add film for protection of the core
 various opening methods like tear open slot, tear open strap, peel and for the aid in insertion into rectum.
off strap "long", peel off strap "short" 2. Vaginal Compressed Tablet - in addition to the active ingredient, it
contains lactose and/or phosphoric acids for adjusting the acidity
Preparing and Pouring of the Melt of the vagina to an approximate pH 5.
Using the least possible heat, the weighed suppository base material is
melted, generally over a water bath. Other Inserts (rectally, Vaginally, & Urethrally)
The medicinal substance are usually incorporated into portion of the melted 1. Tablets & capsules - Vaginal Tablets/Inserts
base by mixing on glass or porcelain tile with spatula, stir and allowed to cool 2. Ointments, Creams, & Aerosol Foams - ProtoFoam
almost to its congealing point.
3. Jellies & Gels
It is generally best to chill the mold in the refrigerator before pouring the
4. Contraceptive Sponge
melt. Then, the melt is placed carefully and continuously in the filling of
each cavity in the mold. 5. Intrauterine Progesterone Drug Delivery System - Progestasert
The pouring must be continuous to prevent “layering” which may lead to a 6. Powders
product easily broken on handling. 7. Solutions - vaginal Douches
When solidified the excess material is scraped off the top of the mold with 8. Enemas - Retention & Evacuation Enemas
spatula. The mold is placed in the freezer to hasten hardening of the 9. Suspensions - Barium Sulfate Suspension
suppository.
When suppositories are hard, the mold is removed from the freezer and
PACKAGING AND STORAGE
dislodged the suppositories from the mold.
Generally, little pressure is required to let fall the suppository of their mold. 1. Glycerin Suppository – tightly close glass container
2. Suppositories prepared with cocoa butter – wrapped individually
3. Suppositories containing light sensitive – individually wrapper –
2. Preparation By Compression
metallic foil
Suppositories may be prepared by forcing the mixed mass of the suppository
base and the medicament into special molds using suppository making 4. Commercially suppositories – individually wrapped – foil or plastic
machines. 5. Some packaged with continuous strips
On a small scale, a mortar is heated in warm water before use and then 6. Cocoa butter –300C
dried, the softening of the base and the mixing process are greatly facilitated 7. Glycerinated – 200C to 250C
forming a paste-like consistency. 8. Polyethylene glycol – room temperature
The compression process is especially suited for making suppositories which
9. With humidity- absorbed moisture and tend to become spongy
contain substances that are heat labile and for suppositories containing a
10. With excessive dryness – lose moisture and become brittle
great deal of substances insoluble in base.
The suppository mass is placed in the cylinder which is then closed, pressure
is applied from one end, by turning wheel and the mass is forced out of the ALPROSTADIL URETHRAL MICROSUPPOSITORY
other end into the suppository mold or die. When the die is filled with the MUSE
mass, a movable end plate at the back of the die is removed and when - single use in male urethra
additional pressure is applied to the mass in the cylinder, the formed - Medicated pellet measuring 1.4 mm in diameter by 3 mm or 6
suppositories are ejected.
mm long
- Administered by inserting the applicator tip after urination
Advantages of Compression: - Available strength are 125, 250, 500, & 1000ug
1. The method is simple - For Erectile Dysfunction
2. The resulting suppository is more elegant than that of hand
molding Rectal Suppositories
3. Avoid the possibilities of sedimentation of the insoluble solids in Suppository Product Effect Category
Bisacodyl Dulcolax local Cathartic
the suppository base
Chlorpromazine Thorazine systemic Anti-emetic,
Disadvantages: tranquilizer
1. Too slow for large scale operation Ergomine tartrate Cafergot systemic Adrenergic
2. Air entrapment in molding fat type base suppositories. This blocking agents
results in uncontrolled weight variation and favors the possible Hydrocortisone Anusol-HC local Pruritis, Inflamed
Hemmarhoids
oxidation of the base and active ingredients.
Indomethacin Indocin systemic Anti-
inflammatory,
Preparation by hand rolling and shaping (no longer used today) analgesic
1. A plastic mass is formed from the base of grated Cocoa butter & Prochlorperazine Compazine systemic Anti-emetic
other ingredients. Promethazine HCl Phenergan systemic Anti-histaminic,
2. Triturate in a mortar, then formed into a ball in the palms of the antiemetic,
sedative
hands, previously cooled in the ice water.

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Vaginal Suppositories g. Gently but firmly push the suppository into the rectum
Product Active Constituents Category until it passes the sphincter (about 1/2 to 1 inch in
AVC suppositories Sulfanilamide, 1.05gm Candida albicans infants, and 1 inch in adults.
infections h. Close your legs and sit (or lay) still for about 15
Betadine medicated Povidone-iodine, 10% relief of vaginitis due
to Candida albicans,
minutes. Avoid emptying bowels for at least one hour
Trichomonas, and (unless the suppository is a laxative). Avoid excessive
Gardnerella vaginalis movement or exercise for at least one hour.
Gyne-Lotrimin Clotrimazole, 100 mg Vulvovaginal yeast i. Wash hands again with soap and warm water
(candida) infections
immediately after inserting the suppository.
Monistat 7 Miconazole nitrate, 200g Antifungal for
vulvovaginal 2. Vaginal
candidiasis a. Wash your hands carefully with soap and warm water.
(moniliasis) b. Remove any foil or plastic wrapping from suppository.
Semicid vaginal nonoxynol-9,100 mg Non-systemic c. Place suppository in applicator.
contraceptive insert reversible method of
d. Hold the applicator by the opposite end from where
birth control
Sultrin vaginal tablet Sulfathiazole, sulfacetamide Haemophilus the suppository is.
sulfabenzamide, 500 mg vaginalis vaginitis e. Either lay on your back with your knees bent, or stand
Terazol 3 Terconazole, 80 mg Antifungal for with your feet spread a few inches apart and your
vulvovaginal knees bent.
candidiasis
f. Gently insert the applicator into the vagina as far as it
(moniliasis)
will go comfortably. Once you are ready, push the
Other examples: inside of the applicator in and place the suppository as
far back in the vagina as possible.
 Miconazole 7
g. Remove the applicator for the vagina.
 Clotrin-V
h. Wash your hands again with soap and warm water.
 Encare (for birth control)

JELLIES
Examples of supp.:
- class of gels in which the structural coherent matrix contains a
high portion of liquid usually water
- usually formed by adding a thickening agent: tragacanth or CMC
- usually clear and uniform semisolid consistency
- Example of Jellies
 Lidocaine HCl Jelly
 Cyclomethycaine Sulfate Jelly
 Promoxine HCl Jelly – local anesthetic
 Ephedrine Sulfate Jelly - symphatomimetic

 Anucort HC 25mg
 Hemril-HC 25mg
 Cotecxin supp.
 Hemmorhoidal-HC 25mg

Administration
1. Rectal
a. If possible, go to the toilet and empty bowels.
b. Wash hands carefully with soap and warm water.
c. Remove any foil or plastic wrapping from the
suppository.
d. Lubricate the tapered end of the suppository with a
small amount of K-Y® Jelly. If the jelly is not available,
moisten the suppository with a small amount of water.
e. Either stand with one leg on a chair, or lay on one side
with one leg straight and the other leg bent toward
your stomach.
f. Separate buttocks to expose the rectal area.

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