Suppository

SUPPOSITORY

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SUPPOSITORY

"Suppositories are specially shaped solid dosage form to be inserted into the body cavities other than mouth to produce a local or systemic effect".

Some examples of body cavities are the rectum, vagina, urethra, nasal cavities, and ear. Suppositories consist of active pharmaceutical ingredients and suppository bases that melt in body cavities or dissolve in the body cavities fluid to release APIs. They are available in various shapes, sizes, weights and consistency. Normally their weight varies from 1 gm to 2 gm.

Advantages

1. Suitable for drugs irritating GIT, nausea and vomiting.

2. Suitable for drugs destroyed in the stomach,

3. Suitable for drugs destroyed in first-pass metabolism.

4. Suitable for unconscious patients, children or old aged patients who cannot swallow the oral dosage form.

5. Most suitable for drugs to produce local effects inside body cavities.

6. Self-administration.

7. Suitable for postoperative patients.

8. Suitable to carry high-dose of the drug.

9. Suitable for lymphatic delivery of drugs.

10. Constant rate of absorption of the drug.

11. Suitable for targeted delivery of drugs

Disadvantage:

1. Not comfortable Patients may feel inconvenienced psychologically. It requires privacy to administer.

2. Self-administration is difficult for arthritic patients.

3. It may melt and leak during transportation and storage.

4. Unpredictable absorption to produce a systemic effect

5. Irritate mucus membrane on repeated administration.

Uses of suppositories (Indications):

They are commonly used to produce local effects such as lubrication, soothing, antiseptic, astringent, or local anaesthetic effects. Suppositories are administered through the rectal route to produce the systemic effect of medicaments

Compile by Alok Bains.

SUPPOSITORY

Compile by Alok Bains.

Uses of suppositories (Indications):

They are commonly used to produce local effects such as lubrication, soothing, antiseptic, astringent, or local anaesthetic effects. Suppositories are administered through the rectal route to produce the systemic effect of medicaments.

Types of Suppositories

1. Rectal suppository: Rectal suppositories are meant for insertion into the rectum to produce a local or systemic effect. It is tapered at one or both ends and swollen slightly before the middle. This shape helps for easy insertion of the suppository into the rectum and its retention inside the rectum. Its weight varies from 1 gm to 2 gm. The size of a suppository for a child is smaller than for an adult.

2. Vaginal suppositories (Pessaries): Pessaries are meant for insertion into the vagina to produce a local effect. They are larger than rectal pessaries. They are conical, rod-shaped or wedge-shaped and their weight varies from 3 gm to 6 gm. They are inserted into the vagina by using fingers or by applicators. They are mainly used to produce antiseptic, local anaesthetic, antibacterial, or contraceptive effects.

3. Urethral suppositories (Urethral bougies): They are meant for insertion into the urethra to produce local effects. They are long, thin, cylindrical, pencil shaped rounded at one end. It is very rarely used

   For males: They are about 100 mm to 150 mm long and weigh about 4 gm for males.

   For females: Their length for females is 60 mm to 75 mm and weighs about 2 gm. 

4. Nasal suppositories (Nasal bougies or buginaria): They are meant for insertion into the nasal cavity. Their length varies from 9 to 10 cm and weigh 1 gm. They are prepared by using a glycerol-gelatin base.

5. Ear suppository (Ear cones or aurinaria): They are meant for insertion into an ear prepared by using theobroma oil as a suppository base. They are rarely used. Urethral bougies molds are used to prepare ear cone and cut according to size.

6. Special suppositories

   a. Tablet suppositories: A suppository formulated by using a compression-like tablet is called a tablet suppository. Normally, rectal suppositories and vaginal suppositories are available as tablet suppositories. A tablet suppository meant for rectal application is called a rectal tablet. A tablet suppository meant for vaginal insertion is called a vaginal tablet. They are available in almond shapes. The almond shape makes the tablet suppository easy to be inserted into the rectum or vagina. It also increases surface area to ease the disintegration of the suppository after insertion into the vagina or rectum. It is coated with polyethene glycol (PEG) to facilitate suppository insertion and also it protects the suppository from the external environment during storage.

   b. Layered suppositories: Drugs are dispensed as suppositories in different layers. Incompatible drugs, drugs with different melting points or drugs with different dissolution rates are dispensed as a layered suppository. It is prepared by molding. One drug is molded as a suppository. After its solidification other drug is added into the same mould. It is also allowed to be solidified. This will form a layer of drugs in one suppository.

   c. Coated suppositories: A Suppository is dipped into a coating solution to develop a layer of coat on the suppository. Examples of coating materials are polyethene glycol, cetyl alcohol, etc. The coating protects the suppository from the external atmosphere during storage, develops lubrication and controls the disintegration of the suppository after insertion into body cavities.

   d. Capsule suppositories: Suppositories prepared by using a gelatin capsule is called capsule suppository. Liquids, semisolids and solid drugs can be dispensed as capsule suppositories.

   e. Disposable moulds suppository: Conventional suppository mould is prepared by using a metallic mould. Then suppository is wrapped individually and dispensed in an outer packing. Disposable moulds suppository is prepared in disposable plastic mould or disposable tin foil mold. These disposable moulds containing suppositories are packed in an outer covering and dispensed.

Advantage:

If a suppository melts during transportation or storage then it can be used for its re-solidification by its cooling. This is not possible in the conventional suppository.

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SUPPOSITORY

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Suppository bases

A suppository base is a vehicle to carry medicament or medicaments which remain solid, firm and in shape during storage transportation and melt or dissolve in body fluids after its administration into body cavities.

Properties of ideal suppository bases:

1. Good appearance

2. Melt at the body temperature or easily dissolve in the body fluid.

3. Retain shape and size during storage and transportation

4. No physical or chemical changes during storage and transportation

5. Attain the shape and size of the mold easily.

6. Does not stick with the wall of the mold.

7. Compatible with medicaments.

8. Release medicaments readily.

9. Thermo stable.

10. Non-toxic and non-irritant.

No single suppository base is available that possesses all the characteristics. Various suppository bases are mixed to develop a suppository base of the required quality.

Types of suppository bases:

Suppository bases are of the following four types depending upon physical properties and their composition. Oleaginous bases, Water miscible bases, and Emulsifying bases.

1. Oleaginous bases (Oily bases):

   a. Cocoa butter (Theobroma oil): It is a yellowish-white solid obtained from the roasted seed of Theobroma Cocoa. Chemically, it is a mixture of glyceryl ester of stearic acid, palmitic acid, oleic acid, and other fatty acids. It has butter-like consistency that melts at a temperature30 to 35 degrees C.

   Advantages: It is the most commonly used suppository base for rectal suppository due to the following properties

   I) It is solid at room temperature and melts at body temperature,

   ii) Non-irritating to mucous membrane.

   iii) It acts as an emollient on the mucous membrane.

   iv) It rapidly melts down on warming and rapidly solidifies on cooling.

   v) It releases medicaments rapidly and is compatible with several medicaments.

   Disadvantages 

   I) It is not suitable for suppositories to be inserted into the vagina, urethra or nasal cavities because it is not miscible with the mucous secretions of these cavities and has a tendency to leak out.

   ii) It requires lubricants

   iii) Variation in physical properties

   iv) It forms soft suppositories with several drugs such as chloral hydrate, phenol, volatile oils, etc.

   v) Fast rancidity,

   vi) To be stored in a dark place and cool temperature to protect from rancidity and melting.

   b. Emulsified theobroma oil: Emulsification of theobroma oil using emulsifying agents produces emulsified theobroma oil. It may be an o/w or w/o type emulsion. Commonly used emulsifying agents are 5% glyceryl monostearate, 2% lecithin, 2% cholesterol, 10% lanette wax, 4% beeswax, 12% spermaceti wax, 4% bees wax etc. It is used to add large amounts of aqueous solution contents to the suppository. It promotes the diffusion and absorption of APIs in the surrounding tissues.

   c. Hydrogenated oil: Hydrogenated vegetable oils, Hydrogenated coconut oil, Hydrogenated peanut oil, Hydrogenated kernel oil, etc are solid fat. They are used as substitutes for theobroma oil. They have several advantages over theobroma oil

   Advantages

   1. Does need special storage conditions and remain solid at room temperature

   2. Overheating does not affect their solidification temperature.

   3. Does not require mould lubrication.

   4. Quick settling inside mould.

   5. Good water holding capacity

   6. Produce colourless, odourless, and polished suppositories.

   7. Very low susceptibility to rancidity and oxidation.

   Disadvantages

   1. The low viscosity of melted Hydrogenated oil thus API may settle down during the solidification of suppository

   2. Brittle suppository upon refrigerated cooling.

2. Water miscible bases:

   a. Glycero-gelatin: It is a mixture of glycerin, water and gelatin. The thickness of the glycerol gelatin base depends upon the concentration of gelatin. The amount of gelatin is adjusted as per the requirement of preparing the suppository. It is a hydrophilic suppository base that dissolves slowly inside aqueous mucous secretion inside the body cavity. It also releases APIs slowly and continuously for a longer duration. It is the most suitable suppository base for the vaginal suppository. However, it is suitable for all types of suppositories. It does not melt at body temperature. It is soluble in the body cavity’s secretions.

   Glycero-gelatin suppository base BP recommends gelatin 14 gm, glycerin 70 gm, and purified water q.s. 100gm. It can accommodate 20% of solid or liquid APIs. Two types of gelatin can be used as an ingredient in a glycero-gelatin base. These are type-A and Type B. Type A is acidic and suitable for acidic APIs. Type B is alkaline and suitable for alkaline APIs.

   Disadvantages

   1. It acts as a laxative,

   2. Variable dissolution time varies from batch to batch and with ageing.

   3. Hygroscopic that develops dryness in the body cavities.

   4. Promote microbial growth.

   5. Require mould lubrication.

   6. Incompatible with several APIs.

   7. Less viscous after melting thus APIs may settle down during solidification

   8. Rapid (refrigeration) cooling makes it brittle.

   b. Soap glycerin: It consists of soap, glycerin and purified water. The interaction of stearic acid and sodium carbonate is used to produce soap. It is harder than glycerol gelatin base due to the replacement of gelatin by soap. It can accommodate about 95% of glycerine. Its main disadvantage is its hygroscopic property. Thus it should be stored protected from moisture in a dry place on wax paper or tin foil.

   c. Polyethylene glycol (PEG or Macrogol or Carbowax or polyglycol): There are several grades of PEG depending upon their molecular weight. Their viscosity increases with the increase in molecular weight. PEG with a molecular weight higher than 1000 is solid wax. PEG with molecular weights 200 to 1000 is in liquid form. PEG of required viscosity and melting point can be prepared by mixing different grades of PEG.

   Advantages

   1. Physiologically inert and stable compounds.

   2. Does not promote microbial growth.

   3. Does not require mould lubrication,

   4. Good solvent property.

   5. Storage at room temperature as the melting point is about 42 degrees C.

   6. Desirable viscosity to reduce leakage problem.

   Disadvantages:

   1. Hygroscopic.

   2. Incompitible with severaIs.

   3. Drug retention is due to good solvent property that reduces the therapeutic effect of drugs.

   4. Brittle suppository.

3. Emulsifying bases

   a. Mass esterinum:

   b. Witepsol

   c. Massupol Suppositories

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SUPPOSITORY

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Preparation of suppository: It is prepared by using the following three methods

1. Hand rolling: It is the oldest method and is not in use.

2. Hot press or Fusion: It requires a suppository mould to prepare a suppository. Suppository moulds are made of stainless steel, nickel-copper alloy, brass, aluminium or plastic. One suppository mould may have 6 to 12 cavities of desired shape and size. Suppository mould for commercial production of suppository may contain 500 cavities of desired shape and size. The suppository mould has two plates attached through a screw. They can be separated longitudinally from each other for cleaning and lubrication purposes. Cleaning should be carried out carefully to avoid any scratch on the inner side of suppository mould cavities and the surface of the mould. Following steps are followed to prepare a suppository using the hot press method.

   a) Mould lubrication: Lubrication of suppository mould cavities shall be required to produce a suppository with a smooth surface. The nature of the lubricant selected shall depend upon the suppository bases to be used. However, some suppository bases do not require lubricants to produce suppositories with a smooth surface.

   Oily lubricant will not serve the purpose if cocoa butter is used as a suppository base. It requires aqueous lubricant oily lubricants will not work.

   Reason: because it will absorb oily lubricant. Lubricants shall not be available in between the wall of suppository mould cavities and the suppository surface. Aqueous lubricant is prepared by mixing soap 5 gm, glycerol 5 gm and Alcohol 90% v/v q.s. 25 ml. Similarly, an aqueous lubricant will not work if the suppository base is glycerol-gelatin. It will require oily lubricants such as liquid paraffin or arachis oil. Emulsifying bases or PEG are suppository bases then lubricants are not required.

   Lubricants are applied inside suppository mould cavities by using a soft brush or swab made of gauze. Cotton wool should not be used because it shades fibres that may stick with the wall of suppository mould cavities. Excessive lubrication should also be avoided.

   b) Mould calibration: Normally, the suppository mould capacity is 1 gm. But the weight of the suppository formed by using suppository mould depends upon the density of the suppository base and APIs used. Thus suppository mould must be calibrated before the preparation of the suppository. Suppositories are prepared by using a suppository base alone then weight average weight of the suppository is calculated. This will be the true weight of the suppository by using that suppository base.

   c) Displacement values calculation: The volume of the suppository remains the same but its weight will depend upon the densities of ingredients used. Thus it requires some adjustment to get a suppository of uniform weight. For this purpose displacement value is calculated. “Amount of API displaces one part of suppository base is called displacement value of API”.

Calculation: Prepare 6 suppositories containing 200 mg of aminophylline in each suppository. The displacement value of aminophylline is 1.5 for theobroma oil.

The weight of one suppository is 1 gm. Thus, the weight of 6 suppositories shall be 6 gm. The total quantity of aminophylline used is 6X 200 = 1800 mg = 1.8 gm

1.5 gm of aminophylline will displace 1 gm of theobroma oil.

1 gm of aminophylline will displace 1/1.5 gm of theobroma oil.

1.8 gm aminophylline will displace 1/1.5 X 1.8 = 1.2 gm of theobroma oil.

Thus, the actual quantity of theobroma oil will require 6 – 1.5 = 4.5 gm.

Determination of displacement value:

1. Prepare and weigh 6 suppositories containing theobroma oil. Let it is “a” gm

2. Prepare and weigh 6 suppositories containing 40% of API. Let it is “b” gm.

3. Calculate the amount of theobroma oil present in the medicated suppositories. Let it is “c” gm.

4. Calculate the amount of API present in the medicated suppositories. Let it is “d” gm.

5. Calculate the amount of theobroma oil displaced by the API. It will be (a-c) gm.

6. The displacement value of API shall be d/(a-c)

d) Procedure: Clean the suppository mould thoroughly. Lubricate its cavity if the suppository base requires mould cavity lubrication. Put it on the ice slab in an inverted position to drain out extra lubricant.

Do calculations for medicaments and suppository base considering displacement value for some extra suppositories. It is done to compensate for the unavoidable loss of ingredients during the preparation of the suppository. Add a suppository base to a porcelain dish. Heat it in a water bath to melt two third of the ingredients. Remove it from the water bath and stir thoroughly till the whole mass meltdown. This step prevents overheating of the suppository base.

Place the calculated amount of medicament on a hot ointment slab. Put half a portion of the melted suppository. Rub and mix them thoroughly using a flexible spatula to make a uniform mixture. This prevents the formation of lumps in the mixture.

Put them into a porcelain dish and heat them by using a water bath with constant stirring. Mixture weight becomes pourable. Transfer melted mass into cooled suppository mould cavities with continuous stirring and till mixture overflows. Stirring assure uniform distribution of medicaments in the suppository. Overflowing of the mixture from the mould cavity prevents the formation of a hollow mass on the top of the suppository. Hollow mass forms due to a decrease in the volume of suppository based on cooling.

Allow to cool down over ice slab and remove excess mixture present over cavities by using a hot spatula. Allow cooling on an ice slab or in a cool place for 10 to 15 minutes. It will form a solid mass. Open the suppository mould and collect the suppositories.

3.  Cold press method: Calculate the amount of medicaments and suppository base considering displacement value. Calculate for some extra suppositories to compensate for the loss of ingredients during the preparation of suppositories.

   Mix the medicament with an equal amount of suppository base. Mix all ingredients by using geometrical mixing. Press them into mould cavities and compress them. Collect the pressed suppository.

   This method is not suitable for suppository base that requires melting to prepare suppository for example glycerol gelatin. It is mainly used for thermolabile medicaments.

Packaging and storage: Wrap the suppository in wax paper or tin foil. Place them inside a cardboard box in an upright position. Place them in such a manner there should be no contact between the two suppositories. The suppository prepared by using glycerol gelatin suppository base is packed in a glass or plastic container. Always store them in a cool place.

Label: “Not for oral application” “Store in a cool place.” “For rectal use only” or “For vaginal use only” or as per the type of suppository.

Compile by Alok Bains.

SUPPOSITORY

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Evaluation of suppositories

1. Weight uniformity: Weigh 20 suppositories. Calculate the average weight of the suppository. Weigh each suppository individually. Variation is weight from the average weight should not be more than 5%.

2. Melting test (Macromelting range test): The time required to melt the entire suppository at 37 degrees C is called melting time. Tablet disintegration test apparatus USP is used to find out the melting time of the suppository.

3. Liquefaction time: It is performed to find out softening time of the suppository. A U-tube apparatus is used to find out the liquefaction time of the suppository. A suppository is placed inside the U-tube apparatus. The U-tube apparatus is immersed in a water bath at a temperature of 37 degrees C. A glass rod is placed over the suppository. The time required to pass through the suppository is noted as the liquefaction time or softening time test. It is mainly used for the rectal suppository.

4. Brittle test (Fragility test): It determines the strength of the suppository. It gives an idea about the ability of the suppository to withstand mechanical force during packing, transportation, and handling of the suppository.

5. Disintegration/dissolution: Dissolution test apparatus for tablets is used to determine the dissolution time of the suppository.

Compile by Alok Bains.