Stability Of Suppository

Suppository must be stable at room temperature to be a suitable dosage form. Suppository is a solid dosage form containing one or more active ingredients and is used to deliver the medication in the body cavities such as the rectum/vagina. They are made up of drug substances (also called the active pharmaceutical ingredient [API]) usually with excipients.

Data on the physical and chemical characteristics and other properties of the drug substance are helpful for designing methods that indicate the drug product's stability and are also helpful in designing formal stability studies.

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Drug stability refers to the extent to which a drug substance or product retains, within specified limits and throughout its period of storage and use, the same properties and characteristics that it possessed at the time of its manufacture.

The type of stability is generally divided into chemical, physical, microbiological, therapeutic, and toxicological. Drug stability can be categorized as pre-market and commercial (marketed product) stability.

Pre-market stability, which supports the clinical trial where drug products are stored under different conditions for safety and efficacy evaluation, is usually conducted throughout the clinical trial and during the filing period.

Commercial stability is continuous assurance on the post-approval batches for long-term stability monitoring on the drug product. Drug stability assessment generally involves the testing of the drug substance or drug product using a stability-indicating method in order to establish the retest period (for pre-market stability) and shelf life (for commercial stability).

Suppository stability

Stability considerations in dispensing practice for suppositories also include observations on excessive softening and oil stains on packaging. Compounded suppositories can be checked for calculations of theoretical and actual weight and weight variation, color, hardness, surface texture, and overall appearance.

Suppository quality control includes physical and chemical aspects of the product. Physical analysis includes visual examination (physical appearance), uniformity of weight, uniformity of texture, melting point, liquefaction time, melting and solidification time, and mechanical strength. Chemical testing includes analysis of the activity and dissolution testing.

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The uniformity of texture can be assessed by sectioning a suppository longitudinally and laterally, and ensuring that each section presents a smooth, uniform surface.

Factors That Affect Stability Of Suppository

These suppositories can be composed of, but not limited to, cocoa butter, coconut oil, glycerinated gelatin, hydrogenated vegetable oils and hard fats, polyethylene glycols (PEGs) and fatty acid esters of PEG. With a combination of these excipient bases, suppositories have fallen into one of two major types: lipophilic based or hydrophilic based.

The lipophilic fat-based (theobroma) suppositories melt at body temperature to release drugs to the body. They readily solubilize typical insoluble small-molecule drugs and require no localized fluids to spread and release drugs. Typically, such suppositories are ideal for the rectum where there is little available fluid in the lower large intestinal tract. 

The hydrophilic water-based suppositories are unaffected by body temperature and require water to dissolve the suppository and release the drug. In contrast to the fat-based suppositories, hydrophilic suppositories can more easily support drug delivery of soluble drug compounds and use the body fluids to dissolve the suppository to transport the drug into the body.

Such water-based suppositories are appropriate for vaginal application where there is more local fluid. Therefore, these two different types of suppositories have allowed this dosage form to become increasingly specific for drug delivery.

Temperature

i. At typical room temperatures of 15–25°C (59–77°F), theobroma oil is a hard, amorphous solid, but at 30–35°C (86–95°F) (i.e., body temperature) it melts to a bland, nonirritating oil. Therefore, in warm climates, these suppositories are required to be stored under refrigeration.

ii. However, the most prominent disadvantage of theobroma oil is its polymorphism. Theobroma oil makes an ideal melting suppository base due to a melting point near human body temperature. In this state, theobroma oil is in its β-crystalline form. However, if the theobroma oil is overheated, the structure is converted to a much less stable β‘-crystal form with a melting point of 26°C.

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iii. There is also another problem. The drug substance can change the temperature of a mixture. When it increases the temperature, the theobroma oil will be converted. 

Moisture

The hydrophilic class of suppositories include excipients that dissolve in the presence of water. These include primarily glycerin, gelatin and water soluble polymers such as PEG. Hydrogel-based suppositories are very hygroscopic and thus must be stored in sealed containers or packaging to prevent absorption of the atmospheric moisture and dissolve. On exposure to moisture, they dissolve, losing shape and form. This can be noticed in the packaging.

Other Ingredients

We merely looked at the suppository base. Just the way temperature and moisture can affect the base, so also any other matter can affect any other ingredients added to a suppository.