What Is a Suppository?

Suppository refers to a solid preparation with a certain shape made of a drug and a suitable matrix for administration in the human cavity. Suppositories are solid at normal temperature. After being inserted into the cavity, suppositories can rapidly soften or dissolve in secretion at body temperature, and gradually release the drug to produce local or systemic effects.

Chinese name: Suppository
Foreign name: Suppository
Department: In human cavity

Types of: Semi-solid preparation
Function: Lubricating, astringent, antibacterial, insecticidal
Classification: Anal plug, vaginal plug, urethral plug

Definition of suppositories

Suppository refers to a solid preparation of a certain shape for intraluminal administration made of a drug and a suitable matrix. Suppositories are solid at normal temperature. After being inserted into the cavity, suppositories can rapidly soften or dissolve in secretion at body temperature, and gradually release the drug to produce local or systemic effects. Early people believed that suppositories only had local effects such as lubrication, convergence, antibacterial, insecticidal and local anesthesia. Later, it was found that suppositories can still exert systemic effects through rectal absorption of drugs, and avoid the first-pass effect of the liver.

Suppositories

Suppositories by route of administration

They are divided into rectal, vaginal and urethral suppositories, such as anal plugs, vaginal plugs, urethral plugs, dental plugs, etc. The most commonly used are anal plugs and vaginal plugs. In order to adapt to the application part of the body, the properties and weight of suppositories are different, and generally have clear regulations.

1. Anal plug Anal plug has conical, cylindrical, torpedo and other shapes. Each one weighs about 2g, is 3-4cm long, and about 1g for children. Among them, the torpedo shape is better. After being inserted into the anus, it is easy to press into the rectum due to sphincter contraction. Drugs in anal suppositories can only exert local therapeutic effects.

2. Vaginal plugs Vaginal plugs are spherical, oval, duckbill-shaped, etc. Each weighs about 2-5g and has a diameter of 1.5-2.5cm, among which the duckbill-shaped surface area is the largest.

3. There are male and female urethral plugs. The weight for men is about 4g and the length is 1-1.5cm; the weight for women is about 2g and the length is 0.60-0.75cm.

The weight of the suppositories mentioned above is made with cocoa butter as a matrix. If the specific gravity of the matrix is different, the weight of the suppositories will also be different.

Suppositories are classified according to preparation technology and release characteristics

1. Double-layer plugs: one type contains different drugs on the inner and outer layers, and the other two layers are on the upper and lower layers, which use water-soluble or fat-soluble substrates to separate different drugs in different layers and control the melting of each layer to make the drugs different Release speed.

2. Hollow plug: can achieve the purpose of rapid drug release. The hollow part is filled with various solid or liquid drugs, and the dissolution rate is faster than that of ordinary suppositories.

3. Controlled and slow-release plugs: microcapsule type, skeleton type, osmotic pump type, gel sustained-release type.

Characteristics of suppositories

The characteristics of suppositories are:

The drug is not damaged by the pH or enzymes of the gastrointestinal tract; Avoid the irritation of the gastric mucosa by the drug;

Intravenous absorption of the middle and lower rectum can avoid the first pass effect of the liver;

suitable for patients who can not or do not want oral administration;

It can play local functions such as lubrication, antibacterial, insecticidal, astringent, analgesic, and itching in the cavity;

Suitable for drugs that should not be taken orally.

Suppository route

The route of absorption of drugs in suppositories: The main routes of absorption of drugs in suppositories are:

The drug enters the liver through the superior rectal vein, enters the liver through the portal vein, and is metabolized before it enters the human circulation.

The drug passes through the inferior rectal vein and anal vein, bypasses the liver through the internal iliac vein, and directly enters the systemic circulation from the inferior vena cava to play a systemic role.

The drug is absorbed through the rectal lymphatic system.

Suppository base

Requirements for suppository bases

The suppository base upon request:

It should have appropriate hardness at room temperature. When it is inserted into the cavity, it will not deform and crack, and it will be softened, melted or dissolved easily at body temperature;

Does not react with the main drug and does not affect the content determination of the main drug;

Non-irritating, non-toxic and non-allergic to mucous membranes;

Stable physical and chemical properties, not prone to mildew during storage and not affecting bioavailability, etc .;

It has wetting and emulsifying properties, and can mix more water.

Types of suppository bases

Suppositories are usually divided into greasy and water-soluble bases.

1. Greasy substrate

(1) Cocoa soy fat: Cocoa soy fat is homogeneous and multi-variable, and has three crystal forms of , , and . Among them, the two crystal forms of and are unstable, the melting point is low, and the type is stable.

(2) Semi-synthetic or fully synthetic fatty acid glycerides: Semi-synthetic coconut oil esters, semi-synthetic behenyl esters, and semi-synthetic palm oil esters are commonly used. Fully synthetic fatty acid glycerides include propylene glycol stearate and the like.

2.Water-soluble and hydrophilic matrix

(1) Glycerin gelatin: This product is made of gelatin, glycerin and water. It has elasticity, is not easy to break, and does not melt at body temperature, but it can be slowly dissolved in secretion. The dissolution rate of the drug can vary with water, gelatin, and glycerin. The proportions of the three are different, and the higher the content of glycerol and water, the easier it is to dissolve.

(2) Polyethylene glycols: It is a type of heterochain polymer polymerized by ethylene oxide. Easy to absorb moisture and deform.

^[1] (3) Non-ionic surfactants: classified by hydrophilic group, there are two types of polyoxyethylene type and polyol type. Polyoxyethylene type, also known as polyethylene glycol type, is the product of the addition reaction of ethylene oxide with compounds containing active hydrogen. Polyol-type nonionic surfactants are ethylene glycol, glycerol pentaerythritol, sorbitan, and An ester of an organic substance containing multiple hydroxyl groups, such as sucrose, and a higher fatty acid. The hydrophilic group in the molecule is a hydroxyl group, and because the hydroxyl group has weak hydrophilicity, it is often used as an emulsifier. ^[1]

Preparation of suppositories

The most commonly used method for suppositories is the hot melt method.

The process of preparing suppositories by hot-melt method is as follows: melting the matrix, adding drugs (mixing), injection molding, cooling, scraping, and taking out.

First, wash and dry the plug mold, and apply a little lubricant to the inside of the model. Then add the drug in different ways according to the properties of the drug, mix well, pour into the plug mold to slightly overflow the mouth of the mold, let it cool, and after it has completely solidified, cut off the overflow part with a knife, open the model, and push the suppository. This method is suitable for the preparation of suppositories of fatty matrix and water-soluble matrix.

(1) How to add suppository drugs:

Suppository Insoluble drugs should generally be pulverized into fine powder, and then mixed with the matrix;

Oil-soluble drugs can be directly dissolved in the melted oily matrix;

Water-soluble drugs can be directly mixed with the melted water-soluble matrix; or absorbed with an appropriate amount of lanolin, and then mixed with a greasy matrix.

(2) Lubricant:

The suppository mold holes need to be lubricated with lubricant to facilitate the removal of suppositories after condensation. There are two common types:

Suppositories with a greasy matrix are usually alcoholic solutions made of 1 part of soap, 1 part of glycerol and 5 parts of 90% ethanol.

Water-soluble or hydrophilic base suppositories are usually oily lubricants, such as liquid paraffin and vegetable oil.

Suppository quality assessment

Sanliu Fuqing suppository (gynecological suppository)

Quality assessment of suppositories:

Unless otherwise specified, it should be stored tightly below 30 to prevent deformation, mildew and deterioration due to heat and moisture.

1. Weight difference:

The inspection of the weight difference limit shall comply with the relevant provisions of the Chinese Pharmacopoeia.

2. Melting time limit:

Measure the time for suppositories to soften, melt or dissolve at body temperature (37 ° C ± 1 ° C).

Methods: Take 3 suppositories, leave them for 1 hour at room temperature, and then check.

The Pharmacopoeia stipulates that suppositories with a greasy matrix should all melt or soften or have no hard core within 30 minutes; suppositories with a water-soluble matrix should be completely dissolved within 60 minutes. If one is unsuccessful, another 3 should be taken for retesting, which should meet the requirements.

3. Microbial limit:

Inspection according to the "Chinese Pharmacopoeia" 2010 "Microbial Limit Inspection Law" shall comply with regulations.

Suppository storage requirements

1. The bases commonly used for suppositories are semi-synthetic fatty acid glycerides, cocoa butter, polyoxyethylene stearate, hydrogenated vegetable oil, glycerin gelatin, polyethylene glycols or other suitable substances. Surfactants can be added to certain matrices to facilitate drug release and absorption by the body.

2. Unless otherwise specified, solid drugs for suppositories should be made into fine powder by appropriate methods in advance, and all should pass through No. 6 sieve. Various suitable shapes are made according to the application cavity and the purpose of use.

3. The drug and matrix in the suppository should be mixed uniformly, the shape of the suppository should be complete and smooth, and it should be non-irritating; after being inserted into the cavity, it should be able to melt, soften or dissolve, and be mixed with the secretion to gradually release the drug and produce local Or systemic effect; and should have appropriate hardness to prevent deformation during packaging or storage.

4. The inner packaging materials used for suppositories should be non-toxic and should not have physical or chemical effects with drugs or matrices. Unless otherwise specified, it should be kept tightly closed below 30 ° C to prevent deformation, mildew and deterioration due to heat and moisture.

Suppository weight difference

The limits of suppository weight differences should meet the following requirements:

Inspection method

Take 10 suppositories and accurately weigh the total weight. After obtaining the average grain weight, weigh each grain accurately. The weight of each capsule is compared with the average weight (for suppositories with labeled kernel weight, the weight of each capsule is compared with the labeled kernel weight), the number of capsules exceeding the limit shall not be more than 1 capsule, and the limit shall not be doubled.

Average weight weight difference limit

1.0g and below 1.0g ± 10%

1.0g to 3.0g ± 7.5%

3.0g above ± 5%

For suppositories that are required to check the uniformity of content, weight difference inspection is generally not performed.