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Chapter 12 – Suppositories

Suppositories

Derived from the Latin term supponere, meaning “to place

under”.

SUB – under ; 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.

Types of Suppositories

1. Rectally

2. Occasionally Urethrally

3. Nasal Insertion

4. Vaginally

5. Rarely aurally

Characteristics based on Administration

1. They have various weights and shapes, the shapes and size of a

suppository must be such that it is capable of being easily inserted

without causing any distension and once inserted must be

retained for the appropriate period of time.

2. Rectal Suppository are usually 32 mm (1 1/2 inches) in length, are

cylindrical, have one or both ends tapered.

3. The USP and NF states that the adult Rectal suppositories weigh

about 2 grams when cocoa butter (theobroma oil), as vehicle, is

employed as based.

Nasal Suppositories - “Burginarium”

- with a glycerinated gelatin base.

Aural Suppositories (“Ear Cones”)

- pencil-shaped suppositories similar in shape to urethral

suppositories but shorter in length, generally about 32 mm

long.

- have been prepared with cocoa butter base

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

enzymes in the GIT

4. Rectal suppositories administered for its systemic effects but

containing drugs destroyed in the liver are better than oral

administration since rectal administration, liver is by passed.

Disadvantage - Inconvenient absorption is irregular and difficult to predict

Local Actions:

Once inserted, the suppository base melts, softens or dissolves, distributing

the medicaments it carries to the tissues of the region.

Rectal Suppositories: relieves constipation or pain irritation, itching and

inflammation associated with hemorrhoids or other anorectal conditions

(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)

Urethral Suppositories: as antibacterial and as a local anesthetic preparatory

to urethral examination

Systemic Actions:

For system effects, the mucous membranes of the rectum and vagina

permits absorption of many soluble drugs.

Rectal suppositories:

Aminophylline & Theophylline - relief of asthma

Prochlorperazine & Chlorpromazine - nausea & vomiting, & as

tranquilizer

Chloral hydrate -sedative and hypnotic

Oxymorphine HCl - narcotic analgesic

Belladonna & Opium - analgesia and antispasmodic effect

Ergotamine tartrate - migraine syndrome

Aspirin - analgesic and antipyretic

Factors Affecting Drug Absorption of Suppositories

Physiological Factors:

1. 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.

Other conditions: diarrhea, colonic obstruction due to tumors,

tissue dehydration can influence the rate and degree of

absorption

2. Circulation Route - drugs absorbed rectally, unlike those absorbed

orally, by pass the portal circulation during their first pass into the

general circulation, thereby enabling drugs otherwise destroyed

in the liver to exert systemic effect.

The lower hemorrhoidal veins surrounding the colon receive the

absorbed drug and initiate its circulation throughout the body, by

passing the liver.

3. pH and Lack of Buffering Capacity of the Rectal Glands

The rectal fluids are essentially neutral in pH and have no

effective buffer capacity so no chemical change will occur in this

area.

The suppository base has a marked influence in the release of

active constituents incorporated into it.

Cocoa butter melts rapidly at body temperature but immiscible

with body fluids and therefore fails to readily release fat-soluble

drugs.

For systemic drug action, it is preferable to incorporate the

ionized rather than the unionized form of a drug to maximize

bioavailability

4. Physiochemical Factors:

a. Drug

i. Relative solubility of the drug in lipid & in water

ii. Particle size of a dispersed drug

1) Lipid-water solubility - a lipophilic drug that

is distributed in a fatty suppository base in

Suppositories Shape Dimensions

1.Rectal

Suppository

Long, cylindrical and have

one or both ends tapered.

Infant: 1 gram

Adult: 2 grams

2.Vaginal

Suppository

“Pessaries”

Globular, oviform, or conical

shaped.

About 3 to 5

grams

3. Urethral

Suppositories

“Bougies”

Slender, pencil-shaped

suppositories.

For males: 4 g,

100-150 mm long.

Females: 2 g, 60

to 70 mm.

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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

- Molds in common use are made from stainless steel, aluminum,

plastic. The molds which separate into sections generally

longitudinally, are opened for cleaning before and after preparing

a batch of suppository, closed when the melt is poured and

opened again to removed the cold, molded suppository.

Scratches in the molds should be avoided especially the plastic.

Lubrication Of The Molds

- Depending upon the formulation, suppository molds may require

lubrication before the melt is poured to facilitate the clean and

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.

Calibration Of The Molds

It is important the pharmacist calibrate each of his

suppository molds for the suppository bases that

he generally employs to have proper quantity of

medicaments.

a. The suppositories are weighed and the total weight &

average weight of each suppository are recorded.

b. To determine the volume of the mold, the

suppositories are carefully melted in a calibrated

beaker.

c. The volume of the melt is determine for the total

number as well as the average of one suppository.

Suppository Molds and Packaging

1. Aluminum metal molds

come in a variety of cavity sizes and with a variety of

number of cavities per mold

Common sizes vary from 1 g to 2.5 g, and common number

of cavities range from 6 cavities up to 100 cavities

The two halves of the mold are held together with either

nuts or some molds have 1 centered screw.

2. Plastic suppository shells

come in long strips that can be torn into any number of

cavities

These disposable molds do not need any lubrication

regardless of the suppository mixture

available in 1 g to 5 g sizes, and many different colors.

Advantage: if the suppository should melt, it will not run out

of the mold. If the material can congeals again, it will retain

the suppository shape.

3. Flexible rubber molds

can be packaged with the suppository still in the mold.

Generally the mold is placed in a special box.

Determination Of The Amount Of Base Required

1. First Method

o Subtract the volume of the drug substance from the

total volume needed.

For example: If 12 mL of Cocoa butter are required to

fill a suppository mold and if the medicaments in the

formula have a collection volume of 2.8 mL the 9.2 mL

of Cocoa butter will be required. By mutiplying 9.2 mL

times the density of cocoa butter, 0.86 g/mL the

weight result is 7.9 g will required

Another example: For Cocoa butter suppositories

Active ingredient: Aminophylline

Density factor: 1.1

Dosage: 0.5000 gram/suppository

Suppository base: Cocoa butter

Blank weight of suppository: 2.000 grams

Calculations:

2. Second Method

o Requires the following steps:

a. Weigh the active ingredient for the preparation

of a single suppository

b. Dissolve or mix it with a portion of melted base

insufficient to fill one cavity of the mold.

c. Place the mixture to the mold

d. Add additional melted base to the cavity to

completely fill the mold.

e. Remove the suppository from mold and weigh

f. Then subtract the weight of the ingredient from

the total weight of the suppository to get the

amount of the base needed.

g. Then multiplied by the number of suppository

made to get the total base needed.

Preparation of ingredient:

Glycerin

Stearic acid

Sodium carbonate

Water

3. Preparing the mold

4. Base preparation

5. Mxing and pouring

Opening a suppository mold

The suppository mixture is poured into the cavities of a

closed mold. When the suppository mixture has

congealed, the excess mass is removed from the top

surface of the mold & the mold is separated into the

two halves.

An efficient way to separate the mold is to remove the

wing nuts or loosen the centered screw and place the

mold so that the posts rest on the table top.

Then, apply a downward pressure only on the bottom

half of the mold.

A knife or spatula should not be used to pry the two

halves apart. This will damage the matching mold faces

which have been accurately machined to give a tight

seal.

Suppository shells can be opened by peeling apart the

two tabs at the bottom of the shell.

6. Cooling and Finishing

7. Packaging

Suppository packaging

Strip ware

Strips (bars) with 10, 12, 20 or 24 individual cells

with or without punching

one side target printing

0.5000/1.1 = 0.4545 g weight of cocoa butter which should be

replaced by 0.5 g of the drug

2.000 g - 0.4545 = 1.5455 g weight of cocoa butter required by

the suppository

0.5000 + 1.5455 = 2.0455 g actual weight of suppository

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white or transparency or one side white and one side

transparency foil

various opening methods like tear open slot, tear open strap, peel

off strap, “short”

Roll ware

with or without perforation between the cells

one or two side target printing

white or transparency or one side white and one side

transparency foil

various opening methods like tear open slot, tear open strap, peel

off strap "long", peel off strap "short"

Advantages of Compression:

1. The method is simple

2. The resulting suppository is more elegant than that of hand

molding

3. Avoid the possibilities of sedimentation of the insoluble solids in

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.

3. A broad bladed spatula or flat board is used to roll it into a

cylinder on a pile tile.

4. Cut with a spatula into sections and shaped as desired.

Compression In A Tablet Press

1. Carbon dioxide - releasing tablet - made up of dried sodium

biphosphate, sodium bicarbonate and starch. This compressed

rectal suppository is dipped or sprayed with a coating of water

soluble polyethylene glycol to add film for protection of the core

and for the aid in insertion into rectum.

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.

Other Inserts (rectally, Vaginally, & Urethrally)

1. Tablets & capsules - Vaginal Tablets/Inserts

2. Ointments, Creams, & Aerosol Foams - ProtoFoam

3. Jellies & Gels

4. Contraceptive Sponge

5. Intrauterine Progesterone Drug Delivery System - Progestasert

6. Powders

7. Solutions - vaginal Douches

8. Enemas - Retention & Evacuation Enemas

9. Suspensions - Barium Sulfate Suspension

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

4. Commercially suppositories – individually wrapped – foil or plastic

5. Some packaged with continuous strips

6. Cocoa butter –300C

7. Glycerinated – 200C to 250C

8. Polyethylene glycol – room temperature

9. With humidity- absorbed moisture and tend to become spongy

10. With excessive dryness – lose moisture and become brittle

ALPROSTADIL URETHRAL MICROSUPPOSITORY

MUSE

- single use in male urethra

- Medicated pellet measuring 1.4 mm in diameter by 3 mm or 6

mm long

- Administered by inserting the applicator tip after urination

- Available strength are 125, 250, 500, & 1000ug

- For Erectile Dysfunction

Rectal Suppositories

Suppository Product Effect Category

Bisacodyl Dulcolax local Cathartic

Chlorpromazine Thorazine systemic Anti-emetic, tranquilizer

Ergomine tartrate Cafergot systemic Adrenergic blocking agents

Hydrocortisone Anusol-HC local Pruritis, Inflamed Hemmarhoids

Indomethacin Indocin systemic Anti-inflammatory, analgesic

Prochlorperazine Compazine systemic Anti-emetic

Promethazine HCl Phenergan systemic Anti-histaminic, antiemetic, sedative

Preparing and Pouring of the Melt

Using the least possible heat, the weighed suppository base material is

melted, generally over a water bath.

The medicinal substance are usually incorporated into portion of the melted

base by mixing on glass or porcelain tile with spatula, stir and allowed to cool

almost to its congealing point.

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 of

each cavity in the mold.

The pouring must be continuous to prevent “layering” which may lead to a

product easily broken on handling.

When solidified the excess material is scraped off the top of the mold with

spatula. The mold is placed in the freezer to hasten hardening of the

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

base and the medicament into special molds using suppository making

machines.

On a small scale, a mortar is heated in warm water before use and then

dried, the softening of the base and the mixing process are greatly facilitated

forming a paste-like consistency.

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.

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

other end into the suppository 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.

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Vaginal Suppositories

Product Active Constituents Category

AVC suppositories Sulfanilamide, 1.05gm Candida albicans infections

Betadine medicated Povidone-iodine, 10% relief of vaginitis due to Candida albicans, Trichomonas, and Gardnerella vaginalis

Gyne-Lotrimin Clotrimazole, 100 mg Vulvovaginal yeast (candida) infections

Monistat 7 Miconazole nitrate, 200g Antifungal for vulvovaginal candidiasis (moniliasis)

Semicid vaginal contraceptive insert

nonoxynol-9,100 mg Non-systemic reversible method of birth control

Sultrin vaginal tablet Sulfathiazole, sulfacetamide sulfabenzamide, 500 mg

Haemophilus vaginalis vaginitis

Terazol 3 Terconazole, 80 mg Antifungal for vulvovaginal candidiasis (moniliasis)

Other examples:

Miconazole 7

Clotrin-V

Encare (for birth control)

Examples of supp.:

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.

g. 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

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

- 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