Chapter 12 – Suppositories Local Actions:
Once inserted, the suppository base melts, softens or dissolves, distributing
Suppositories
Derived from the Latin term
supponere,
meaning “to place
under”.
inflammation associated with hemorrhoids or other anorectal conditions
SUB – SUB – under ; PONERE – PONERE – to place
Are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolved and exert localized or systemic effects.
Suppositories
the medicaments it carries to the tissues of the region. Rectal Suppositories: relieves constipation or pain irritation, itching and
Shape
(pinworms, dermatitis) Vaginal suppositories: as antiseptic in feminine hygiene and as specific agents
to combat an invading pathogen. (vaginitis - by Trichomonas vaginalis and Candida albicans)
Dimensions
Urethral Suppositories: 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
2.Vaginal
Globular, oviform, or conical
About 3 to 5
permits absorption of many soluble drugs.
Suppository
shaped.
grams
Rectal suppositories:
Systemic Actions:
For system effects, the mucous membranes of the rectum and vagina
“Pessaries”
Aminophylline & Theophylline - relief of asthma
3. Urethral
Slender, pencil-shaped
For males: 4 g,
Suppositories
suppositories.
100-150 mm long.
Prochlorperazine & Chlorpromazine - nausea & vomiting, & as tranquilizer Chloral hydrate -sedative and hypnotic
Females: 2 g, 60
“Bougies”
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.
5. Rarely aurally
Colonic content - When systemic effects are desired from the
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
1.
Other conditions: diarrhea, colonic obstruction due to tumors,
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 without causing any distension and once inserted must be 2. 3.
absorption 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
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.
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.
Nasal Suppositories Suppositories - “Burginarium” -
pH and Lack of Buffering Capacity of the Rectal Glands
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 ( “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: 1.
When a drug cannot be tolerated, cause to vomit orally
2.
When a drugs cannot be swallowed - causing choking
3.
When a drug may be decomposed or inactivated by the pH or
4.
ionized rather than the unionized form of a drug to maximize bioavailability 4.
Physiochemical Factors: a.
Drug
enzymes in the GIT
i.
Relative solubility of the drug in lipid & in water
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 administration since rectal administration, liver is by passed.
1)
Lipid-water Lipid-water solubility solubility - a lipophilic drug that
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
5)
escape to the surrounding aqueous fluids
allow to congeal.
than would a hydrophilic substance present
ii.
in fatty base to an extent approaching the
Bases of polyethylene glycols Polyethylene Glycol
saturation.
1)
Ex.: polyethylene glycols - which dissolve in
2)
prepared to various chain lengths, molecular weights, and physical
both water-soluble and oil-soluble drugs.
states. They are available in a number
Particle size - For drugs present in the
of molecular weights ranges 200, 400,
suppository in the undissolved state, the
600, 1000, 1500, 1540, 3350, 4000, 6000 & 8000.
amount release and dissolved in absorption.
2)
of 200, 400, and 600 are clear,
readily the dissolution of the particle and
colorless liquids. Those greater than
the greater t he he chance for rapid absorption”
1000 are wax like, white solids with hardness increasing with an increase
i.
Ability to melt, soften or dissolve at body temperature
ii.
Ability to release the drug substance
iii.
It is hydrophilic or hydrophobic character
in molecular weight. Ex.: Polybase ***Glycerinated gelatin based suppositories have
Nature of the base: must be capable of
tendencies to absorb moisture due to the hygroscopic
melting, softening, or dissolving to release
nature of glycerin causing the following effect:
its drug components for absorption. 2)
Undesirable Characteristics Of A Base a)
That which interact with the
Ex.: Jell-O -
drug inhibiting its release such that the drug absorption will be
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)
prevented or delayed. b)
a.
That which is irritating to the mucous membranes of the
distearate esters of mixed polyethylene diols & the
rectum thus initiating a colonic
free glycols) b.
with emulsifying agents capable of forming W/O
prospect of thorough drug
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.
Classification Of Suppository Bases
Fatty or Oleaginous bases a.
When a base is not specified, Cocoa Butter is used
b.
Other oleaginous materials: i. ii.
iii.
Preparations Of Suppositories
1.
Molding from a melt/Fusion (Pour Molding)
Hydrogenated fatty acids of vegetable oils - palm,
2.
Cold Compression (No heat Application)
kernel oil, and cotton seed oil
3.
Hand molding/rolling and shaping (No Heat Application)
Fat bases compounds - glycerin with the higher
4.
Compression in a tablet press
molecular weight fatty acids: palmitic and stearic
*** The method most commonly employed in both small scale and industrial
acids
molding. scale is molding.
Example of Suppositories with Cocoa Butter as a Base
Preparation By Molding
1)
Cotmar
2)
Dehydag
3)
Wecobee
4)
Witepsol
5)
Fattybase
1.
The main members of this group are based of i.
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.
Glycerinated gelatin
USP Preparation Of Glycerinated Gelatin
Melting of the base preferably in water or steam bath to avoid local overheating.
Water-soluble or water-miscible bases a.
-
Mixtures of many fatty acids (including Cocoa Butter)
movement, negating the release and absorption.
2.
Mixture of oleaginous and water-soluble materials Ex.: Polyoxyl 40 stearate (mixture of monostearate &
response and prompt a bowel
1.
Polyethylene glycols with average MW
“The smaller the particle size, the more
Suppository base
1)
polymers of ethylene oxide and water,
the anorectal fluids, release for absorption
size of the particle will influence the
b.
Pour the melted mixture into molds &
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.
1)
Weigh medicinal substance
2)
Add water to make 10 grams
Note: Suppositories of cocoa butter, glycerinated gelatin, polyethylene
3)
Dissolved or mix 20 mL of glycerin and
glycol and most other suppository bases are suitable for preparation by
20 g of granular gelatin.
molding. molding .
4)
Heat on a steam bath until all gelatin dissolved
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Density factor: 1.1
Suppository Molds
-
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 coco a 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 0.5000 + 1.5455 = 2.0455 g actual we ight of suppository
easy removal of the molded 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 Requires the following steps:
o
Calibration Of The Molds
a. It is important the pharmacist calibrate each of his
of a single suppository
suppository molds for the suppository bases that
b.
he generally employs to have proper quantity of The suppositories are weighed and the total weight &
c.
Place the mixture to the mold
d.
Add additional melted base to the cavity to
average weight of each suppository are recorded. b.
c.
Dissolve or mix it with a portion of melted base insufficient to fill one cavity of the mold.
medicaments. a.
Weigh the active ingredient for the preparation
completely fill the mold.
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
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
1.
2.
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
Plastic suppository shells
3.
Preparation of ingredient:
Aluminum metal molds
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
wing nuts or loosen the centered screw and place the
the suppository shape.
mold so that the posts rest on the table top.
Flexible rubber molds
An efficient way to separate the mold is to remove the
of the mold. If the material can congeals again, it will retain
can be packaged with the suppository still in the mold.
Then, apply a downward pressure only on the bottom 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 Amount Of Base Required
1.
which have been accurately machined to give a tight
First Method o
seal.
Subtract the volume of the drug substance from the
total volume needed.
Suppository shells can be opened by peeling apart the 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 Another example : For Cocoa butter suppositories
Active ingredient: Aminophylline
Strips (bars) with 10, 12, 20 or 24 individual cells
with or without punching
one side target printing
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white or transparency or one side white and one side
3.
cylinder on a pile tile.
transparency foil various opening methods like tear open slot, tear open strap, peel
A broad bladed spatula or flat board is used to roll it into a
4.
Cut with a spatula into sections and shaped as desired.
off strap, “short” Compression In A Tablet Press
Roll ware
1.
Carbon dioxide - releasing tablet - made up of dried sodium
with or without perforation between the cells
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 of the vagina to an approximate pH 5.
Preparing and Pouring of the Melt
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, st ir and allowed to cool
2.
Ointments, Creams, & Aerosol Foams - ProtoFoam
almost to its congealing point.
3.
Jellies & Gels
4.
Contraceptive Sponge
It is generally best to chill the mold in the refrigerator before pouring the melt. Then, the melt is placed carefully and continuously in the filling 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 dislodged the suppositories from the mold. Generally, little pressure is required to let fall the suppository of their mold.
2. Preparation By Compression
Suppositories may be prepared by forcing the mixed mass of the suppository
PACKAGING AND STORAGE
1.
Glycerin Suppository – tightly close glass container
2.
Suppositories prepared with cocoa butter – wrapped individually
3.
Suppositories containing light sensitive – individually wrapper – metallic foil
base and the medicament into special molds using suppository making
4.
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 –30 C
dried, the softening of the base and the mixing process are greatly facilitated
7.
Glycerinated – 20 C to 25 C
forming a paste-like consistency.
8.
Polyethylene glycol – room temperature
9.
With humidity- absorbed moisture and tend to become spongy
10.
With excessive dryness – lose moisture and become brittle
The compression process is especially suited for making suppositories which contain substances that are heat labile and for suppositories containing a great deal of substances insoluble in base.
Commercially suppositories – individually wrapped – foil or plastic 0
0
0
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 remo ved 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.
Advantages of Compression:
1.
The method is simple
2.
The resulting suppository is more elegant than that of hand
3.
mm long -
Administered by inserting the applicator tip after urination
-
Available strength are 125, 250, 500, & 1000ug
-
For Erectile Dysfunction
molding
Rectal Suppositories
Avoid the possibilities of sedimentation of the insoluble solids in
Suppository Bisacodyl Chlorpromazine
Product Dulcolax Thorazine
Effect local systemic
Ergomine tartrate
Cafergot
systemic
Hydrocortisone
Anusol-HC
local
Indomethacin
Indocin
systemic
Prochlorperazine Promethazine HCl
Compazine Phenergan
systemic systemic
the suppository base Disadvantages:
1.
Too slow for large scale operation
2.
Air entrapment in molding fat type base suppositories. This results in uncontrolled weight variation and favors the possible oxidation of the base and active ingredients.
Preparation by hand rolling and shaping (no longer used today)
1.
A plastic mass is formed from the base of grated Cocoa butter & other ingredients.
2.
Triturate in a mortar, then formed into a ball in the palms of the hands, previously cooled in the ice water.
Category Cathartic Anti-emetic, tranquilizer Adrenergic blocking agents Pruritis, Inflamed Hemmarhoids Antiinflammatory, analgesic Anti-emetic Anti-histaminic, antiemetic, sedative
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g.
Vaginal Suppositories Product AVC suppositories
Active Constituents Sulfanilamide, 1.05gm
Betadine medicated
Povidone-iodine, 10%
Gyne-Lotrimin
Clotrimazole, 100 mg
Monistat 7
Miconazole nitrate, 200g
Semicid vaginal contraceptive insert
nonoxynol-9,100 mg
Sultrin vaginal tablet
Sulfathiazole, sulfacetamide sulfabenzamide, 500 mg Terconazole, 80 mg
Terazol 3
Category Candida albicans infections relief of vaginitis due to Candida albicans, Trichomonas, and Gardnerella vaginalis Vulvovaginal yeast (candida) infections Antifungal for vulvovaginal candidiasis (moniliasis) Non-systemic reversible method of birth control Haemophilus vaginalis vaginitis Antifungal for vulvovaginal candidiasis (moniliasis)
Gently but firmly push the suppository into the rectum until it passes the sphincter (about 1/2 to 1 inch in infants, and 1 inch in adults.
h.
Close your legs and sit (or lay) still for about 15 minutes. Avoid emptying bowels for at least one hour (unless the suppository is a laxative). Avoid excessive movement or exercise for at least one hour.
i.
Wash hands again with soap and warm water immediately after inserting the suppository.
2.
Vaginal a.
Wash your hands carefully with soap and warm water.
b.
Remove any foil or plastic wrapping from suppository.
c.
Place suppository in applicator.
d.
Hold the applicator by the opposite end from where the suppository is.
e.
Either lay on your back with your knees bent, or stand with your feet spread a few inches apart and your knees bent.
f.
Gently insert the applicator into the vagina as far as it will go comfortably. Once you are ready, push the inside of the applicator in and place the suppository as
Other examples:
Miconazole 7
Clotrin-V
Encare (for birth control)
far back in the vagina as possible. g.
Remove the applicator for the vagina.
h.
Wash your hands again with soap and warm water.
JELLIES
Examples of supp.:
-
class of gels in which the structural coherent matrix contains a high portion of liquid usually water
Anucort HC 25mg
Hemril-HC 25mg
Cotecxin supp.
Hemmorhoidal-HC 25mg
-
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
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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