Suppositories

The mucosal route of drug administration is divided into seven membrane surfaces characterized as [blank_start]otic[blank_end], [blank_start]ophthalmic[blank_end], [blank_start]nasal[blank_end], [blank_start]oropharyngeal[blank_end], [blank_start]urethral[blank_end], vaginal, and rectal.

Suppositories are sometimes preferred because it evades the [blank_start]first pass effect[blank_end] that happens in the liver

Vaginal inserts are often compounded with [blank_start]water[blank_end]-soluble bases such as [blank_start]polyethylene glycol[blank_end] to minimize leakage

Rectal suppositories are [blank_start]cylindrical[blank_end] or [blank_start]conical[blank_end]. Approximately 2 g and are about 2 to 3 cm long

Vaginal inserts are [blank_start]ovoid[blank_end] or [blank_start]globular[blank_end] shaped. The weigh about [blank_start]3[blank_end] to [blank_start]5[blank_end] g

Urethral inserts vary depending on whether it is for male or female. Males - They are [blank_start]5 mm[blank_end] in diameter, [blank_start]125 mm[blank_end] in length, and [blank_start]4 g[blank_end] in weight Females - They are [blank_start]5 mm[blank_end] in diameter, [blank_start]50 mm[blank_end] in length, and [blank_start]2 g[blank_end] in weight

The choice of a particular melting range is dictated by the influence of other components that influence the final melting range of the product. In general, suppository bases melt between [blank_start]27[blank_end] and [blank_start]45[blank_end] degrees

Hard fat suppository bases are mixtures of [blank_start]semisynthetic triglyceride esters[blank_end] of longer-chain fatty acids.

[blank_start]Hydrophilic suppository[blank_end] bases are mixtures of hydrophilic [blank_start]semisolid[blank_end] materials that in combination are solid at room temperature and yet release the drug by melting, erosion, and dissolution when administered to the patient

[blank_start]Polymorphic[blank_end] drugs are treated as different drugs because they display different properties. An example is [blank_start]cocoa butter[blank_end] which should not be heated over [blank_start]35[blank_end] degrees.

Cocoa butter has no [blank_start]surfactant[blank_end], and therefore, cannot emulsify water. Some substances such as chloral hydrate tend to lower the melting point of CB. It may be necessary to add [blank_start]beeswax[blank_end] to raise the melting point.

Water-soluble ionized salt forms of drugs that have [blank_start]high[blank_end] base partition coefficients should be used when possible with cocoa butter particularly when a [blank_start]systemic effect[blank_end] is desired.

Newer synthetic triglycerides such as [blank_start]palm kernel[blank_end] and [blank_start]coconut oils[blank_end] have [blank_start]emulsification[blank_end] properties, do not exhibit [blank_start]polymorphism[blank_end] like cocoa butter. However, they are more expensive

[blank_start]Glycerinated gelatin[blank_end] is a useful suppository base for vaginal inserts. Used for sustained release over a long period

[blank_start]Glycerin[blank_end] is categorized in the NF as a [blank_start]humectant[blank_end], plasticizer, solvent and tonicity-adjusting agent

For suppositories in the body, there is either melting or erosion (dissolution). The erosion may be favorable for those who want [blank_start]prolonged release[blank_end]

PEG bases are incompatible with a large number of drugs, especially those prone to [blank_start]oxidation[blank_end]. PEG also interacts with some plastics such as [blank_start]polystyrene[blank_end] which is used in some prescription vials, which is why suppositories are wrapped in foil or in plastic bags

Several surfactants closely related chemically to polyethylene glycols can be used as suppository vehicles. Examples of these are polyoxyethylene [blank_start]sorbitan fatty acid esters[blank_end] and [blank_start]polyoxyethylene stearates[blank_end]

One major advantage of substances such as polyoxyethylene sorbitan fatty acid esters and polyoxyethylene stearates as suppository vehicles is their [blank_start]water dispersibility[blank_end]

Cocoa butter melts quickly at body temperature and is [blank_start]immiscible[blank_end] with body fluids. This [blank_start]inhibits[blank_end] the diffusion of fat-soluble drugs to the affected sites.

[blank_start]Polyethylene glycol[blank_end] is a suitable base for some antiseptics

Glycerinated gelatin is seldom used rectally because of its [blank_start]slow dissolution[blank_end]

When selecting a suppository base, fatty bases exhibit the following:

When selecting a suppository base, PEG exhibits the following:

[blank_start]Hand Rolling[blank_end]: - Plastic-like mass is prepared by triturating grated cocoa butter and active ingredients in a mortar - The mass is formed into a ball in the palm of the hands then rolled into a uniform [blank_start]cylinder[blank_end] - The cylinder is then cut into a number of pieces which are rolled to produce a [blank_start]conical[blank_end] shape

Advantages to Hand Rolling are the following:

Disadvantages of Hand Rolling are the following:

[blank_start]Fusion Molding[blank_end]: - First, melt the suppository base - Dispersing the drug in the melted base - Remove from the heat and pour into a supp. mold - After [blank_start]congealing[blank_end], the suppositories are removed from the mold - Metal molds must be [blank_start]lubricated[blank_end]!!

[blank_start]Compression Molding[blank_end]: Mixed mass of suppository base and the drug is forced into a special compression molds

Density factor = Weight of [blank_start]drug[blank_end] / Weight of [blank_start]base displaced[blank_end]

When DF is unknown, you can determine is via double casting method: - Take [blank_start]50[blank_end]-[blank_start]60[blank_end]% of base and pour all the drug you need into the mold - And then take the rest of the base ([blank_start]nonmedicated[blank_end]) and fill it to the top - Allow it to cool down - Cut off excess base - Take suppositories out, re-melt and pour again - Calculating for excess is important because the base will [blank_start]contract[blank_end]