Solid Dosage Forms: Suppositories

What are suppositories?

Solid dosage forms intended for administration of drug via the rectum that melt, soften, or dissolve in the body cavity

What are pessaries?

Vaginal suppositories

What are bougies?

Urethral suppositories

Are suppositories for systemic or local application?

Both

Local uses of suppositories

For treatment of haemorrhoids, itching, or infections

Systemic uses of suppositories

Used to deliver drugs such as:

• Anti-nausea drugs

• Anti-asthmatic drugs

• Analgesics

• Hormones

What are the limitations of suppositories?

Bioavailability can vary between individuals due to differences in venous drainage and absorption

When are suppositories useful?

• Infants and small children

• Severely debilitated patients

• Patients unable to take medicines orally

• Patients unsuitable for parenteral (injectable) administration

Are suppositories more common in continental Europe or UK/USA?

Continental Europe

What physiological factors affect rectal drug absorption?

• The rectum contains only a small amount of fluid (3 mL), so there is limited liquid available for drugs to dissolve in.

• Poorly soluble drugs dissolve slowly, which slows their absorption.

• Rectal fluid has a near-neutral pH (7–8), so most drugs are not significantly ionised by pH changes.

• Rectal fluid has little buffering capacity, meaning its pH does not strongly resist changes.

How are suppositories formulated and what bases are used?

• Suppositories are made by dissolving or dispersing the drug in a melted base at elevated temperature.

• The mixture is poured into a mould and allowed to solidify at room temperature.

What kind of bases are used?

• Coca butter - A fatty base

• Glycogelatin - An aqueous base

How does drug solubility influence the choice of suppository base?

Drug release from a suppository depends on how soluble the drug is in the base (vehicle)

The drug must leave the base and partition into rectal fluid before it can be absorbed

If a drug is very soluble in the base, it tends to remain there, so release into rectal fluid is slower

How does particle size affect drug release from suppositories?

• For drugs present as undissolved particles in suppositories, particle size affects the rate of dissolution and drug absorption.

• Smaller particles have a larger surface area, so they dissolve more quickly.

• Faster dissolution leads to faster absorption of the drug.

• Ideally, particle size should be less than 50 µm to reduce local irritation.

What are the physical chemistry of drug influences the choice of base?

qBase must be capable of melting, softening, or dissolving to release its drug content for absorption.

qIf base interacts with drug and inhibits release, absorption may be impaired or even prevented.

qFurthermore, if base irritates rectal membrane, it may initiate bowel movement resulting in incomplete drug release and absorption.

What are the ideal properties of a suppository base?

Melts at body temperature or dissolves in body fluids.

Non-toxic and non-irritant.

Compatible with any medicament.

Releases any medicament readily.

Easily molded and removed from the mold.

Stable when heated above its melting point.

Easy to handle.

Stable on storage.

Water-soluble bases

Glycogelatin

• Used exclusively for laxative purposes or vaginal therapy

• Dehydrating effects on mucosa can lead to local irritation

• Long preparation time

• Lubrication of mold is required

What are the advantages of using mixtures of PEGs as suppository bases?

• Suppository melting point can be adjusted to withstand exposure to warmer temperatures

• Release of drug is not dependent on melting point

• Physical stability on storage is improved

• Suppositories are readily miscible with rectal fluids

What are the disadvantages of using mixtures of PEGs as suppository bases?

• Chemically more reactive than fats. Incompatible with many drugs (e.g., Penicillin G).

• Care required in processing to avoid inelegant contraction holes in the suppositories.

• Release rate of water-soluble drugs decreases with increasing MW of the PEG used.

• PEGs tend to be more irritating to mucous membranes than fatty bases.

How are suppositories packaged?

• Packed in tin, aluminum, paper, or plastic

• Poorly packaged suppositories may cause staining, break, or deform by melting

• Both coca butter and glycerol gelatin suppositories are preferably stored in a fridge

• PEG suppositories can be stored at room temperature (w/o refrigeration)

What are displacement values (DVs)?

Incorporated drug alters suppository density, almost always increasing final weight.

If dose is specified as “drug weight per suppository”, difference between the suppository weight comprising the base alone and that with the drug must be determined.

This calculation requires knowledge of the displacement value (DV) of the drug relative to the base used.

DVs in literature are usually given for Oil of Theobroma.

If glycogelatin (~1.2-times more dense) is used, an appropriate correction is needed.