Suppositories
Definition:
Suppositories are solid dosage forms intended for insertion into body cavities, such as the
rectum, vagina, or urethra, where they dissolve, soften, or melt to exert local or systemic effects.
The medicament is incorporated into the suppository base and product is formulated in such a
way that it dissolves or melts and is absorbed into the blood stream. They are used to deliver
both systemically and locally acting medications. They are available in various shapes and sizes.
Types of Suppositories:
1. Rectal Suppositories:
o Shape: Cylindrical or conical.
o Use: Local effects (e.g., treatment of hemorrhoids) or systemic effects (e.g.,
antipyretics, antiemetics).
2. Vaginal Suppositories (Pessaries):
o Shape: Oviform or globular.
o Use: Local effects, such as treatment for infections or hormone replacement
therapy.
3. Urethral Suppositories (Bougies):
o Shape: Slender and pencil-like.
o Use: Local treatment of urethral infections or erectile dysfunction.
4. Nasal and Ear Suppositories (Rare):
o Use: Local effects, such as decongestants.
Advantages:
1. Can exert both local and systemic effect
2. Used to promote evacuation of bowel
3. Avoid any gastrointestinal irritation
4. Bypasses First-Pass Metabolism: Suitable for drugs that are extensively metabolized in
the liver when taken orally.
5. Alternative to Oral Administration: Useful for patients who cannot take medications
orally due to vomiting, dysphagia, or unconsciousness.
6. Local Action: Provides targeted therapy with minimal systemic side effects (e.g., for
hemorrhoids or vaginal infections).
7. Controlled Drug Release: Provides prolonged therapeutic action by slow dissolution or
melting.
8. Ease of Administration: Non-invasive and self-administered.
9. Post operative patients can easily be given suppository.
Disadvantages:
1. Patient Compliance: Some individuals find suppositories uncomfortable or
embarrassing to use.
2. Storage Issues: Heat-sensitive suppositories may require refrigeration.
3. Unpredictable Absorption: Rectal and vaginal mucosa may have variable drug
absorption due to pH, fluid content, or motility.
4. Irritation: Some excipients or drugs may irritate the mucosa.
5. Cannot be given to patients suffering from diarrhea
6. Limitations in Drug Type: Not suitable for all drugs, particularly those that require very
precise dosing or have poor solubility in the base.
Types of suppository base
IDEAL SUPPOSITORY BASE
1. Melt at body temperature or dissolves in body fluids
2. Non toxic and non irritant
3. Compatible with other medicaments
4. Releases any medicament readily
5. Easily moulded and removed from the mould
6. Stable to heating above the melting point
7. Easy to handle
8. Stable on storage
The bases can be classified as follows
1. Fatty or Oleaginous Bases
These bases are derived from fats and oils, with cocoa butter (theobroma oil) being the most
traditional.
a) Cocoa butter/Theobroma oil
Properties:
It is a yellowish white solid obtained from crushed seeds of Theobroma cocoa. It is a
mixture of glyceryl esters of stearic, oleic ,palmitic and other fatty acids
It has butter like consistency.
Its melting point is 30-35°C. It melts at body temperature and release the medicament for
rapid absorption.
It is readily liquefied on warming and rapid settling on cooling.
It is a best suitable base for rectal suppositories.
Advantages:
Non-irritating to mucous membranes.
Smooth texture provides good patient acceptability.
Excellent release of lipophilic drugs.
Disadvantages:
Leakage from body cavities
Polymorphism: Cocoa butter can crystallize in different forms, leading to variations in
melting point.
become rancid (oxidation) and melt in warm weather
tendency to stick to the sides of the moulds when solidified (lubrication of mould
required)
Poor water absorption capacity, limiting hydrophilic drug release.
b) Emulsified Theobroma oil (Addition of emulsifiers)
This may be used as a base when large quantities of aqueous solutions are to be
incorporated. The use of 5% Glyceryl stearate, 10% lennette wax and 2-3% cetyl alcohol and
12% spermaceti are recommended to prepare Emulsified Theobroma oil suppositories
c). Hydrogenated oils
These are obtained by hydrogenation of various vegetable oils e.g. Arachis oil, cotton seed
oil, coconut oil, palm oil etc.
Advantages:
Resistant to oxidation.
Lubrication of mould is not required.
Emulsifying and water absorbing capacity are good.
Disadvantages:
Suppositories become brittle on rapid cooling in refrigerator.
2. Water soluble and water miscible bases
a) Glycero-gelatin bases
It is a mixture of glycerin and water which is made stiff by addition of gelatin. The stiffness
can be manipulated by adjusting the quantity of gelatin. Glycerogelatin base B.P. contains
14%w/w of gelatin and 70%w/w of glycerol. These bases dissolve in body fluids rather than
melting. Suppositories prepared are translucent which tend to dissolve and disperse slowly in the
body cavity and release the drug (more prolonged release)
Advantages:
Stable over a wide temperature range.
Provide a longer shelf life than fatty bases.
Disadvantages:
Dissolving time may vary on the amount of gelatin
Gelatin is incompatible with many drugs
More chances of microbial growth
Hygroscopic in nature (require special storage)
Can cause irritation to mucous membranes due to their hygroscopic nature (glycerinated
gelatin cause dehydration).
The base itself show laxative action
b). Soap glycerin base
These are prepared by mixing soap and glycerin as soap is used as hardening material. Sodium
stearate soap can be with 95% glycerin as a base.
Advantages:
Stable over a wide temperature range.
Provide a longer shelf life than fatty bases.
Disadvantages:
Hygroscopic in nature (require special storage)
The base itself show laxative action
c). Polyethylene Glycols/ Carbowaxes / polyglycols / Macrogols
Macrogols with M.W. less than 1000 are liquids and those with M.W more than 1000 are
solids.
Advantages:
Melting point is above 420 C, hence cool storage is not required. Can be easily used in hot
climate.
Suppositories formed are clean and smooth
Chemically stable
Non irritant
no bacterial growth
Hardness can be varied by changing the proportion of high and low M.W. Macrogols
High melting point , Do not melt but dissolves (prolonged action)
Do not stick to mould
Provide a longer shelf life than fatty bases.
Disadvantages:
Hygroscopic in nature (require special storage)
Incompatible with few drugs
These have solvent property which results in retention of drugs in the liquefied base thus
reducing its therapeutic activity.
3. Emulsifying bases
They are proprietary synthetic bases. Non ionic surfactants are added in these bases to
incorporate both hydrophillic and lipophillic drugs
They are not rancid
Do not adhere
Good water absorbing capacity
non irritant
compatible with various drugs
Example : Witepsol, Massa Estarinum, Massupol
Methods of Preparation of Suppositories
There are four main methods for preparing suppositories:
1. Hand Rolling Method
This is an older, manual method used for small-scale production or when molds are unavailable.
Steps:
1. Preparation of Base:
o The base (e.g., cocoa butter) is softened but not melted.
2. Incorporation of Drug:
o The drug is mixed with the softened base using mortar and pestle.
3. Shaping:
o The mixture is rolled into cylindrical shapes manually on a flat surface.
o Uniform lengths are cut, and one end is tapered to facilitate insertion.
Advantages:
No need for special equipment.
Suitable for heat-sensitive drugs.
Disadvantages:
Time-consuming and labor-intensive.
Less uniformity in size and shape.
2. Molding (Fusion) Method/Hot process
This is the most widely used method for preparing suppositories. It involves melting the base,
incorporating the drug, and pouring the mixture into molds.
Steps:
1. Melting the Base:
o The base (e.g., cocoa butter, PEG) is melted over a water bath to avoid
overheating.
o Stirring is done to ensure uniform melting.
2. Incorporation of Drug:
oDrugs are added either in soluble form (for soluble drugs) or as a fine powder (for
insoluble drugs).
o Homogeneous mixing is ensured.
3. Pouring into Molds:
o Moulds are available in various shapes and sizes.
o Moulds with 6-12 suppositories are generally available
o Moulds are made up of stainless steel, nickel, copper alloy, brass, aluminum or
plastic
o The mixture is poured into clean, pre-lubricated molds.
o Lubrication is done a brush or cotton swab. Excessive lubrication must be avoided
and can be drained by keeping the mould in inverted position
o Overfilling slightly is recommended to compensate for shrinkage upon cooling.
4. Cooling and Solidification:
o Molds are allowed to cool at room temperature or refrigerated.
5. Trimming and Packaging:
o Excess material is trimmed off.
o Suppositories are removed from molds and packaged individually.
Advantages:
Accurate dosing.
Uniform drug distribution.
Disadvantages:
Heat-sensitive drugs may degrade.
Risk of base segregation during melting.
Calibration of mould
Calibration is necessary because the size (or the volume) of the suppository from a particular
mould is same but the weight varies. This is because the density of different base and
medicament are different. So mould should be calibrated for individual base and medicament.
This is done by preparing a set of suppositories using the base only and weighing the
suppositories and finding the average mean, which will indicate the true capacity of the mould.
Displacement Value (DV)
The displacement value (DV) is a measure used in suppository formulation to quantify how
much of the suppository base is displaced by the active ingredient or other additives. It is crucial
for accurately determining the amount of base required when incorporating drugs into
suppositories. It is defined as number of grams of drug that displaces one gram by weight of the
base. Displacement value is the weight of the drug (in grams) that displaces 1 gram of the
suppository base.
It can be determined by the following method
1) Find the weight of 5 suppositories of plain cocoa butter = a
2) Find the weight of 5 suppositories containing 20% drug = b
𝟖𝟎
3) Calculate the amount of cocoa butter= 𝟏𝟎𝟎 𝑿 𝒃 = 𝒄
𝟐𝟎
4) Calculate the amount of medicament = 𝟏𝟎𝟎 𝑿 𝒃 = 𝒅
5) Calculate the amount of cocoa butter displaced by the medicament = (a-c)
6) Find out the displacement value of the medicament i.e. amount of drug displaces 1 g of
base
𝒅
a. =
𝒂−𝒄
3. Cold Compression Method
This method is useful for the thermolabile and insoluble drugs because heating and stirring of the
base with medicament is not required .This method uses specialized compression equipment and
is similar to tablet compression.
Steps:
1. Mixing:
o Cocoa butter is grated
o The drug and base are thoroughly mixed.
o The mixture should have a semi-solid or plastic consistency.
2. Compression:
o The mixture is compressed into molds using a suppository-making machine.
o The prepared mass is placed in cylinder ‘c’ and forced through a narrow opening
by means of a piston ‘p’
o The threads of mass passing into mould ‘E’ are compressed until a homogenous
fused mass is formed.
o On the removal of retaining stop plate‘S’ the suppositories are ejected by further
pressure.
3. Ejection:
o Suppositories are ejected from the molds after solidification.
Advantages:
Avoids heating, making it suitable for heat-sensitive drugs.
Produces uniform suppositories.
Disadvantages:
Requires specialized equipment.
The mass and compression cylinder of the machine may be chilled to prevent heat of
compression from making the mass too fluid.
Packaging and storage of suppositories
Usually packed in shallow partitioned card board boxes which can uphold them in
upright position and do not allow them to come in contact with each other
Aluminum foil and PVC polythene strip can also be used
Glycero-gelatin suppositories are packaged in tightly closed glass container to protect
from moisture
Storage temperature
Cocoa Butter suppositories- are stored below 300C
Glycero-gelatin suppositories- are stored below 350C
Macrogol suppositories- can be stored at room temperature
Label- “Not to taken “and “FOR RECTAL USE ONLY”
Stability Problems
Blooming: Blooming refers to the appearance of a white or crystalline layer on the surface of
suppositories during storage. It occurs due to the migration of certain ingredients, such as fats or
waxes, to the surface. It shows poor appearance
Hardening: Hardening refers to the gradual increase in the hardness of suppositories over
time,. This happens due to structural changes in the base, such as crystallization or
polymerization. This effects melting and rate of absorption of drugs.
Evaluation of Suppositories
The evaluation of suppositories is crucial to ensure that they meet the required quality standards,
including the correct dose, proper shape, uniformity, stability, and safety for the intended use.
The following tests and evaluations are typically carried out to assess the quality of
suppositories:
1. Visual Inspection
Purpose: To check for physical defects such as cracks, chips, or discoloration.
Procedure: The suppositories are inspected visually under normal or magnified
conditions.
Criteria: Uniform shape and size, no surface defects, and uniform color.
2. Weight Uniformity
Purpose: To ensure that each suppository contains the correct amount of drug and base,
maintaining consistency.
Procedure: A sample of suppositories (usually 10) is weighed individually. The average
weight is calculated, and the variation between individual suppositories is measured.
Criteria: The weight variation should fall within a specific acceptable range, typically
±5% for most formulations.
3. Content Uniformity
Purpose: To confirm that the active pharmaceutical ingredient (API) is evenly
distributed throughout the suppository.
Procedure: A specified number of suppositories (usually 10) are analyzed for their drug
content using appropriate analytical methods (e.g., High-Performance Liquid
Chromatography or UV spectrophotometry).
Criteria: The content of the drug in each suppository should be within ±10% of the
labeled claim.
4. Melting Point Determination
Purpose: To ensure that the suppository melts at body temperature (about 37°C) for
proper drug release.
Procedure: The melting point of the base is determined using a melting point apparatus
or through the drop method. There are two tests
Criteria: The melting point of the suppository should be within a defined range, typically
close to body temperature, with a slight variation depending on the base used.
5. Breakage Test (Test of physical strength):
The tensile strength of suppositories is measured in this test to assess their ability to withstand
the rigors of normal handling. The apparatus used is called the breaking test apparatus. It consists
of a double- wall chamber. Through the walls of the chamber, water is pumped. The inner
chamber consists of a disc that holds the suppositories. To this disc, a rod is attached. The other
end of the rod consists of another disc on which weights are placed.
On the first disc, the test suppository is placed. On the second disc, a 600 g weight is placed.
At 1 minute interval, 200 g weights are added till the suppository crumbles. All the weights used
are added which gives the tensile strength. Likewise, few more suppositories are tested and the
average tensile strength is calculated. Tensile strength indicates the maximum force which
the suppository can withstand during production, packing, and handling. Large tensile
strength indicates fewer tendencies to fracture.
6. Dissolution Test
Purpose: To determine the rate at which the drug is released from the suppository.
Procedure: A specified number of suppositories are placed in a dissolution apparatus
or a dialysis cell containing a dissolution medium, and samples are taken at regular
intervals to measure the concentration of the drug.
Criteria: The drug release profile should meet the required pharmacokinetic properties,
ensuring appropriate therapeutic levels.
7. pH Testing (for Vaginal and Urethral Suppositories)
Purpose: To ensure that the suppository is not acidic or basic to the point of causing
irritation to the mucous membranes.
Procedure: The pH of the melted suppository base is tested.
Criteria: The pH should be within a safe range for the intended site of application (e.g.,
pH 4.5-7.5 for vaginal suppositories).
8. Liquefaction time /softening time
It is the time for which a suppository melts completely at a definite temperature. This test
measures the softening time of suppository which indicates the hardness of base.
A big pipette having a narrow opening on one side and broad opening on other side is
dipped in hot water ( 35 ± 2 0 C). The narrow end facing towards hot water.
Suppository was introduced into the pipette through broad end and pushed down , until it
reaches the narrow end.
A glass rod is allowed to rest on suppository.
The time at which the glass rod reaches to narrow end after complete melting of
suppository represents the liquefaction time.
