Suppositories

Suppositories

A suppository is a solid medical preparation in a roughly conical or cylindrical shape, designed to be inserted into the rectum or vagina to dissolve. It’s a dosage form used to deliver medications by insertion into a body orifice, where it dissolves or melts to exert local or systemic effects. It’s a solid but readily meltable cone or cylinder of usually medicated material for insertion into a bodily passage or cavity (such as the rectum). Suppositories can be used when oral administration is not possible or when a local effect in the rectum or vagina is desired. They are used in various medical conditions and purposes. In this article we will study types, methods of preparation and evaluation of suppositories.

Types of suppositories

• Rectal Suppositories: These are inserted into the rectum and are typically used to treat conditions like constipation, fever, hemorrhoids, mental health issues such as anxiety, schizophrenia, or bipolar disorder, nausea, including motion sickness, and pain.
• Vaginal Suppositories: These are also known as pessaries. These are inserted into the vagina to treat bacterial or fungal infections and vaginal dryness. They are typically oval and come with an applicator.
• Urethral Suppositories: These are inserted into the urethra. In rare cases, men may use a type of urethral suppository to treat erection problems. These suppositories are the size of a grain of rice and deliver a drug called alprostadil.
• Nasal Suppositories: These are inserted into the nose. They are less common and are typically used for local treatment of nasal conditions.
• Ear Suppositories: These are inserted into the ear. They are less common and are typically used for local treatment of ear conditions.

Each type of suppository has its own unique properties and uses in various fields such as medicine.

Advantages

• Avoid First-Pass Metabolism: Suppositories bypass the digestive system, avoiding first-pass metabolism in the liver.
• Localized Action: They can provide localized treatment, reducing systemic distribution.
• Patient Compliance: They can be used in patients who are unconscious or have difficulty swallowing.
• No Gastric Irritation: They do not cause nausea or vomiting due to gastric irritation, which can occur with oral therapy.

Disadvantages

• Patient Acceptance: Some patients may find them uncomfortable or inconvenient to use.
• Storage: They need to be stored in a cool place to prevent melting.
• Hygroscopic Nature: They can become hard on drying and soft in contact with moisture.
• Bacterial Growth: There’s a chance of bacterial growth.
• Incompatibility: They can be incompatible with certain substances.

Remember, the specific advantages and disadvantages can vary depending on the specific characteristics of the suppository.

Suppository bases

Suppository bases are substances used to hold the medicament and release the drug after administration. These bases are used to hold the medicament and release the drug after administration. They have no pharmacological action. They are classified into two major categories as follows.

Fatty Suppository Bases

These bases melt at body temperature. Examples include:

• Theobroma Oil (Cocoa Butter): It’s a yellowish-white solid having a chocolate flavor.
• Semi-synthetic or Synthetic Fatty Acid Glycerides: These are synthetic fats that have certain advantages over theobroma oil.

Hydrophilic Suppository Bases

These bases dissolve or disperse in rectal secretions. They are further classified as,

• Water-Soluble Bases: For example, Polyethylene Glycol (PEG).
• Emulsifying Bases (Water Miscible): These bases emulsify a small amount of aqueous solution of the drug.

Ideal requirements of suppository bases

The ideal suppository base should meet the following requirements.

• Nontoxic, Non-allergenic, and Non-irritating: It should not cause any harm or irritation to the mucous membranes.
• Compatible with a Variety of Drugs: It should be able to incorporate different types of medicaments without causing any chemical or physical instability.
• Melts or Dissolves in Rectal Fluids/Body Cavities: The base should either melt at body temperature or dissolve in body fluids to release the medicament.
• Releases the Medicaments Readily: The base should allow for the efficient release of the medicament.
• Stable on Storage: The base should not undergo any significant changes in its physical or chemical properties over time.
• Does Not Interfere with the Release or Absorption of Drug Substances: The base should not bind or otherwise interfere with the release or absorption of drug substances.
• Stable if Heated Above its Melting Point: The base should not undergo any significant changes in its properties if heated above its melting point.

Easily Molded and Should Not Adhere to the Mold: The base should be easily formed by compression or molding and should not stick to the mold.

Methods of preparations

Suppositories can be prepared using various methods. Here are some of the common methods.

Fusion Molding

This widely used method involves melting the suppository base (e.g., cocoa butter, PEG) and mixing it with the medication. The molten mixture is poured into molds of the desired shape and size. The molds are cooled, allowing the suppositories to solidify into their final form.

Compression Molding

This method uses specialized molds and a compression machine to directly press the powdered suppository mixture (base + medication) into the desired shape. It offers faster production and more consistent suppository weights. However, it requires careful control of pressure and temperature to avoid damaging the mixture.

Hand Rolling

This traditional method is suitable for small batches or specialized shapes. The base and medication are kneaded together into a smooth paste. The paste is rolled into the desired shape and size using gloves or tools. It requires skill and practice for consistent results.

Extrusion

Used for large-scale production, this method involves forcing the suppository mixture through a die of the desired shape. It offers high efficiency and consistency. However, it requires specialized equipment and expertise in extrusion technology.

Suppository Shells

Pre-formed shells made from various materials (e.g., gelatin) can be filled with the medication mixture. This method offers convenience and ease of use, especially for liquid or semi-solid medications. However, it may not be suitable for all medications or desired release profiles.

The choice of method depends on factors like the scale of production, desired properties, and medication characteristics. Proper hygiene and sanitation are essential throughout the preparation process. Accurate weighing of ingredients is crucial for consistent dosage and medication release. Suppositories should be properly stored in cool, dry conditions to prevent softening or melting.

Displacement value

The displacement value (DV) in suppositories is defined as the quantity of drug which displaces one part of the base. It’s an important parameter in suppository formulation and manufacturing, as it helps ensure accurate dosing of the active ingredient.

The DV can be determined experimentally by measuring the weight of base displaced by a known amount of drug. Alternatively, manufacturer-provided DV values for specific base-drug combinations can be used.

Here’s how you can calculate the displacement value,

Let’s say you have

• a base B
• a medicament/drug M
• an amount of pure base suppository (without medicament/drug) a
• an amount of medicament/drug d.

The required amount of base can be calculated as:

c=b×(100−X)​/100

where X is the percentage of the drug in the suppository.

The replacement of drug with base in grams is calculated as, a−c

Therefore, the displacement value is calculated as:

DV=d/(a−c)​

Evaluation of suppositories

Suppositories are evaluated using several tests to ensure their quality, safety, and efficacy. Here are some of the key evaluation tests.

• Uniformity of Weight: Weigh 20 suppositories individually and determine their average weight. Not more than two of the individual weights should deviate from the average weight by more than 5%, and none should deviate by more than 10%.
• Disintegration Test: This test measures the amount of dosage form that gets dissolved in body fluid in unit time. It’s a measure of the rate of drug release from the suppository. Disintegration is complete when molded suppositories are completely dissolved, dispersed into their components, or have become soft. Disintegration occurs in not more than 30 minutes for fat-based suppositories and for water-soluble suppositories disintegration occurs in not more than 60 minutes.
• Content Uniformity Test: Take 10 suppositories and determine the active ingredients of each of the 10 suppositories using a suitable analytical method. If not more than one of the individual values thus obtained is outside the limit i.e.% of the average value and none of them is outside the limit i.e. 25% of the average value.
• Melting Point Determination Test: Both macro melting range and micro melting range are determined. The macro melting range is a measure of the thermal stability of the suppository. The micro melting range of the fatty base is measured in capillary tubes.
• Liquefaction Time (Softening): Softening time is the time for which the suppository melts completely at a definite temperature.
• General Appearance Test: The visual appearance of suppositories is assessed for uniformity in size, shape, and colour. Any discoloration or deformities may indicate a problem with the manufacturing process.
• Assay of Active Contents: The amount of drug present in each suppository is determined to ensure that the correct dosage is being delivered to the patient.
• Test of Drug Uptake/Absorption into Bloodstream: This can be done through both in-vitro and in-vivo tests.

These tests help ensure that suppositories are safe, effective, and suitable for use in the intended patient population.

Summary

Suppositories are solid dosage forms designed to be inserted into body orifices, where they dissolve or melt to release medication. They’re made using bases like fatty bases (e.g., cocoa butter) or hydrophilic bases (e.g., polyethylene glycol). Preparation methods include fusion molding and compression molding. Evaluation tests ensure quality and include uniformity of weight, disintegration test, content uniformity test, melting point determination, liquefaction time, general appearance, assay of active contents, and drug uptake/absorption tests.

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