Suppositories & Pessaries

Be- dilu. A

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 Objectives

After the end of this topic students will be able to:

– Define suppositories and pessaries

– Differentiate between suppositories and pessaries

– Classify suppositories

– Discuss different suppository bases used

– Formulate and prepare suppositories and pessaries

– Discuss applications suppositories and pessaries

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 SUPPOSITORIES & PESSARIES
• Suppositories are solid, single-dose preparations which are intended to
insert body orifice (BP)

– The shape, volume and consistency of suppositories are suitable for

rectal administration

• Pessaries are solid, single-dose preparations

– They have various shapes, usually ovoid, with a volume and

consistency suitable for insertion into the vagina.

– contain one or more active substances dispersed or dissolved in a

suitable bases that may be soluble or dispersible in water or may
melt at body temperature 3
 Cont…
Shape of suppositories

Rectal using Vaginal using

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 Cont…
Dosage form characteristics:

A. Rectal suppositories

– for adults weigh 2 gm and are torpedo shape

– Children's suppositories weigh about 1 gm

B. Vaginal suppositories or Pessaries

– weigh about 3-5gm and are molded in globular or oviform shape or

– compressed on a tablet press into conical shapes

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 Cont…
Character of action

1. Local Action

• Rectal suppositories are mostly employed to treat rectal disease

– to relieve constipation or the pain, irritation, itching, and inflammation associated

with hemorrhoids or other anorectal conditions

• Vaginal suppositories or inserts are employed mainly as contraceptives,

antiseptics in feminine hygiene

– as specific agents to combat an invading pathogen.

• Urethral suppositories: as antibacterial and as a local anesthetic 6

 Cont…
2. Systemic Action

• Administered rectally in the form of suppositories for systemic effects

include:

– for the relief of nausea and vomiting and as a tranquilizer

– for narcotic analgesia

– for the relief of migraine syndrome

– anti-inflammatory analgesic and antipyretic

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 Formulations
• Suppositories are formulated in different shapes and sizes

– usually 1-4 g

• Their drug content varies widely, from less than 0.1% up to 40%

• Generally the suppository consists of a vehicle in which the drug is

incorporated, and in some cases additives are coformulated

– The vehicle (suppository base)

• Q1: If 2g suppository contains 10% of the API of interest,

– What would be the amount of API?

– Given that, the suppository contains only vehicle, find its amount
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 Formulations…
Ideal suppository base:

– Melts at body temperature or dissolves in body fluids

– Non-toxic and non-irritant

– Compatible with any medicament

– Releases any medicament readily

– Easily molded and removed from the mould

– Stable to heating above the melting point

– Easy to handle

– Stable on storage
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 Cont…
Classification of Suppository Bases

• Two main classes of vehicles in use

– The glyceride-type fatty bases and the water-soluble ones

• Although the ideal vehicle has not been found

– the large variety of bases that are available enables a well

considered choice for every drug that has to be formulated as a
suppository

• Choosing the optimum base requires a lot of practical experience

– at present this can only partly be guided by scientifically sound data

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 Cont…
Fatty vehicles
• are the most frequently employed suppository bases
1) Cocoa Butter
– The fat obtained from the roasted seed of
theobroma cacao.
– At room temperature it is a yellowish, white solid
having a faint, agreeable chocolate-like odor
– No longer used because of its many disadvantages
✓ its well known polymorphic behavior
✓ its insufficient contraction at cooling
✓ low softening point, chemical instability
✓ poor water absorptive power and its price
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 Cont…
• Substances such as phenol and chloral hydrate have a tendency to
lower the melting point of cocoa butter when incorporated with it

– it is not feasible to prepare a solid suppository

• Solidifying agents like cetyl esters wax (about 20%) or beeswax (about
4%) may be melted with the cocoa butter to compensate for the
softening effect of the added substance

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 Cont…
Advantages of Cocoa Butter

– A melting range of 30 - 36°C

– Readily melted on warming, rapid setting on cooling

– Miscible with many ingredients

– Non-irritating

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 Cont…
Disadvantages
• Polymorphism
– When melted and cooled it solidifies in different crystalline forms
✓depending on the temperature of melting, rate of cooling and
the size of the mass
– If melted at not more than 36°C and slowly cooled it forms stable
beta crystals with normal melting point
– If over-heated then cooled it produce unstable gamma crystals which
melt at about 15°C or alpha crystals melting at 20°C
– Cocoa butter must be slowly melted over a warm water bath to avoid
the formation of the unstable crystalline form
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 Disadvantages Cont…
– Adherence to the mould

– Softening point too low for hot climates

– Melting point reduced by soluble ingredients

✓ Phenol and chloral hydrate have a tendency to lower the melting point

✓ Solidifying agents incorporated to compensate for the softening effect

– Rancidity on storage
– Poor water-absorbing ability
✓ Improved by the addition of emulsifying agents
– Leakage from the body
– Expensive
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 Cont…
2) Synthetic type of fatty vehicles

• For example: hard fat and hydrogenated vegetable oil

• Offer a number of advantages over cocoa butter

– Their solidifying points are unaffected by overheating

– They have good resistance to oxidation because of the lower content

of unsaturated fatty acids

– The difference between melting and settling points is small

• Hence they set quickly,

• the risk of sedimentation of suspended ingredients is low

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 Cont…
– They are marketed with different melting point ranges

– They contain a proportion of w/o emulsifying agents, and therefore, their

water-absorbing capacities are good

– No mould lubricant is necessary because they contract significantly on

cooling

Disadvantages
– Brittle if cooled rapidly, then avoid refrigeration during preparation

– The melted fats are less viscous than Theobroma oil

✓ As a result greater risk of drug particles to sediment, lack of uniform drug
distribution

✓ localized irritancy 17
 Cont…

Water-soluble and water-miscible bases:

1) Glycero-gelatin

• The commonest is Glycerol Suppositories Base B.P.

– which has 14% w/w gelatin, and 70% w/w glycerol & water Q.S. to 100%

• The glycerol-gelatin base U.S.P.

– consisted of 20% w/w gelatin, and 70% w/w glycerol & water Q.S. to 100%

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 Cont…
Disadvantages:
• A physiological effect
– Osmosis occurs during dissolving in the mucous secretions of the rectum

✓ producing a laxative effect

– Can cause rectal irritation due to small amount of liquid present

– Unpredictable solution time

• Hygroscopic:
– They should be packaged in tight containers

– Have dehydrating effects on the rectal and vaginal mucosa leading to irritation
• Microbial contamination likely
• Long preparation time
• Lubrication of the mould is essential 19
 Cont…
2) Macrogols (polyethylene glycols)

• Polyethylene glycols are polymers of ethylene oxide and water,

prepared to various chain lengths, molecular weights, and physical
states

• The numerical designations refer to the average molecular weights of

each of the polymers

• Polyethylene glycols (PEGs) having average molecular weights of

300, 400, and 600 are clear, colorless liquids, while those with
molecular weights of 600-1000 are semisolids
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 Cont…
• Those having average molecular weights of greater than 1000 are wax-
like, white solids with the hardness increasing with an increase in the
molecular weight
– These polyethylene glycols can be blended together to produce suppository bases
with varying: melting points, dissolution rates and physical characteristics

• Drug release depends on the base dissolving rather than melting

– The melting point is often around 50°C
• Higher proportions of high molecular weight polymers
– produce preparations which release the drug slowly and are also brittle

• Less brittle products which release the drug more readily can be
prepared by mixing high polymers with medium and low polymers
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 Cont…
Preparation of Suppositories
1. Compression
2. Fusion or preparation by mold
Preparation by Compression

– Suppositories may be prepared by forcing the mixed mass of the

suppository base and the medicaments into special molds using
suppository making machines.

– In preparation for compression into the molds, the suppository base

and the other formulated ingredients are combined by thorough
mixing, the friction of the process causing the base to soften into a
paste-like consistency
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 Cont…
a) Cold Compression:
– The process of compression is especially suited for the making of
suppositories containing medicinal substances that are heat labile and

– for suppositories containing a great deal of substances insoluble in the base

b) Hand rolling and shaping:

– With the 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 of the art of the pharmacist

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 Cont…
Fusion or preparation by mold

• Most frequently employed in the preparation of suppositories both on

a small scale and on an industrial scale

Automatic Molding machine:

– All the operations in pour moulding are done by automatic

machines

– Using this machine, up to about 10,000 suppositories per hour can

be produced

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 Cont…

Mold shape

– Molds in common use today are made from stainless steel

– The molds, which separate into sections, generally longitudinally, are

opened for cleaning before and after the preparation of a batch of
suppositories

– Care must be exercised in cleaning the mold for the desired

smoothness of the resulting suppositories

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 Cont…

Mold
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 Cont…
LUBRICATION OF THE MOLD

• Depending upon the formulation, suppository molds may require lubrication

before the melt is poured to facilitate the clean and easy removal of the
molded suppositories

• Lubrication is seldom necessary when the suppository base is cocoa butter or

polyethylene glycol

• Lubrication is usually necessary when glycerinated gelatin suppositories are

prepared

• Any materials which might cause irritation to the mucous membranes should
not be employed as a mold lubricant
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 Cont…
The steps in molding

1. Melting of the base

2. Grinding of ingredients

3. Incorporating of any required medicaments

4. Pouring the melt into molds

5. Allowing the melt to cool and congeal into suppositories

6. Streaming of molds

7. Removing the formed suppositories from the mold

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 Cont…

Pouring the melt into molds Removing the formed suppositories

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 Cont…
Calibration of the mold

• Each individual mold is capable of holding a specific volume of material

in each of its openings

• If the material is changed, the weight of the resulting suppositories will

differ from the weight of suppositories prepared in the same mold

– because of the difference in the densities of the materials

• Similarly, any added medicinal agent would further alter the densities
of the bases, and the weights of the resulting suppositories would be
different from those prepared with base material alone
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 Cont…

• It is important that the pharmacist calibrate each of his suppository

molds for the suppository bases

– that generally employs in order that to prepare medicated

suppositories each having the proper quantity of medicaments
Example 1
• If 12 mL of cocoa butter is required to fill a suppository mold and if the
medicaments in the formula have a collective volume of 2.8 mL, 9.2
mL of cocoa butter will be required
• By multiplying 9.2 mL times the density of cocoa butter, 0.86 g/ mL, it
may be calculated that 7.9 g of cocoa butter will be required
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 Cont…
• Suppositories usually are formulated on a weight basis so that the
medication replaces a portion of the vehicle as a function of specific
gravity
– If the medicinal substance has a density approximately the same as theobroma oil,
it will replace an equal weight of oil
– If the medication is heavier, it will replace a proportionally smaller amount of
theobroma oil

• E.g. Tannic acid has a density factor of 1.6 compared with cocoa butter
– If a suppository is to contain 0.1g tannic acid, then 0.1g ÷ 1.6, or 0.062 g, cocoa
butter should be replaced by 0.1g of drug

– If the blank weight of the suppository is 2.0 g, then 2.0 - 0.062 g, or 1.938 g,
cocoa butter is required per suppository

– The suppository will actually weigh 1.938g + 0.1 g, or 2.038 g

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 Cont…
Example 2
• Prepare 12 acetaminophen 300 mg suppositories using cocoa butter.
The average weight of the cocoa butter blank is 2 g and the average
weight of the medicated suppository is 1.8 g.
– Density factor = B/A- C
where
– A is the average weight of blank,
– B is the weight of medication per suppository, and
– C is the average weight of medicated suppository.or
– Displacement value of the medicament = B / (A - C)
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 Determination of displacement value
• The volume of each suppository mould is known (and has been
calibrated) and therefore the molten formulations are dispensed into
the moulds according to volume

• However, if the drug is dispersed in the molten formulation, the volume

of the formulation will be dependent on the mass of drug present
(remembering that solids displace an equal volume of base).

• To ensure that the correct volume of base is used, a calculation is

performed based on the displacement value
– i.e. the ratio of the weight of the drug to the weight of base displaced by the drug

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 Cont…
• The displacement factor may be visualized as the weight of drug
required to displace unit weight of base

• For example, the displacement value of cinchocaine hydrochloride is

1.5 for cocoa butter (and indeed other triglyceride bases)
– Therefore 1.5 grams of this therapeutic agent will displace 1 gram of cocoa butter

• Example:

– Determine the displacement value for a therapeutic agent in a

triglyceride base. The concentration of drug in each suppository
should be 10%
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 Cont…
• Step 1: Prepare (e.g. six) blank suppositories and weigh. Total weight determined as 6
grams (1 gram per suppository)
• Step 2: Prepare six suppositories containing 10% drug in each suppository (based on the
volume of the suppository mould) and weigh. Asume, Total weight determined as 6.11g
• Step 3: Calculate the masses of base and drug in the six suppositories (remembering that
the drug loading of the suppositories is 10%)
– Base = 90/100x 6.11 = 5.50g
– Drug =10/100x6.11 = 0.61g
• Step 4: Calculate the mass of base displaced by the 0.61 gram of drug
– 6.0 - 5.5 = 0.5g
• Step 5: Calculate the displacement value for the drug
– DV or DF = 0.61/0.50 = 1.22

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 Cont…
• When using suppository bases other than cocoa butter, such as a polyethylene
glycol base, it is necessary to know either the density of the drug relative to
the new base or the densities of both the drug and the new base relative to
cocoa butter
• The density factor for a base other than cocoa butter is simply the ratio of the
blank weights of the base and cocoa butter.
• For instance, if a suppository is to contain 0.1g tannic acid in a polyethylene
glycol base, (polyethylene glycol base is assumed to have a density factor of
1.25)
– Then 0.1g ÷ 1.6 × 1.25, or 0.078 g, polyethylene glycol base should be replaced
by 0.1g drug If the blank weight is 1.75g for the polyethylene glycol base, then
1.75g - 0.078 g, or 1.672 g, of base is required per suppository.
– The final weight will be 1.672g base + 0.1g drug, or 1.772 g
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 Cont…
• Another method for determination of the amount of base in the
preparation of medicated suppositories requires the following steps:
– Weigh the active ingredient for the preparation of a single suppository

– 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

– 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
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 Cont…
• A third method is to 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.
• Packaging and Storage
– Individually wrapped in either foil or a plastic material
– Some are packaged in a continuous strip with suppositories being
separated by tearing along perforations placed between suppositories
– Poorly packed suppositories may give rise to staining, breakage or
deformation by melting.
– maintain in a cool place 39
 Cont…
• Both cocoa butter and glycerinated gelatin suppositories stored
preferably in a refrigerator

• PEG suppositories stored at usual room temperature without the

requirement of refrigeration

Clinical use of suppositories

➢systemic action

➢local action

➢vagina VS rectal route

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 Factors Affecting Absorption
The factors affecting the rectal absorption of a drug

• Physiologic factors

– colonic contents, circulation route, and the pH and lack of buffering

capacity of the rectal fluids

• Physicochemical factors of the drug and the base

– The lipid-water partition coefficient; particle size; nature of the

bases

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 Cont…
Advantages:
– Can exert local effect on rectal mucosa
– Used to promote evacuation of bowel
– Avoid any gastrointestinal irritation
– Can be used in unconscious patients (e.g. during fainting)

– Can be used for systemic absorption of drugs and avoid first-pass

metabolism

– Babies or old people who cannot swallow oral medication

– Post operative people who cannot be administered oral medication

– People suffering from severe nausea or vomiting

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 Cont…

Disadvantages:

– Patient acceptability

– Patients suffering from diarrhea.

– In some cases the total amount of the drug must be given will be
either too irritating or in greater amount than reasonably can be
placed into suppository

– Incomplete absorption may be obtained because suppository

usually promotes evacuation of the bowel

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 Methods of application
– Wash your hands thoroughly with water and soap

– Apply disposable latex gloves or a finger cot

– Make the suppository rigid if it is soft

– Remove the wrapper if present

– Lie on your side

– Insert the suppository into the rectum

– Hold the buttocks together tightly for a few seconds

– Remain lying down for about 5 minutes to avoid having the suppository
come out

– Remove the glove and wash your hands completely 44

Cont’…

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Cont…

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Thank you
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