Lecture 39: Compounding Suppositories: Materials & Tools

What are suppositories?

• Introduced into rectum

• Melt, soften, or dissolve at body temperature

What are inserts?

Introduced into other body cavity other than mouth or rectum

What is the environment of the rectum?

• Constant & static

• Fluid volume 1-3 mL

• Neutral pH of 7-8 w/ minimal buffering capacity

• Relatively small surface area for absorption

• Single layer of columnar cells to form the epithelium

• Goblet cells

What are the 3 hemorrhoidal veins that drain the rectum?

• Superficial- drains upper rectum into portal circulation

• Middle & inferior- drains the lower rectum directly into systemic venous circulation

What can the rectal route minimize first-pass metabolism depending on?

Position of the formulation in the rectum

What does the Porto-systemic shunting & lymphatic draining of rectum play significant role in?

Systemic absorption of lipophilic drugs

What are properties of the rectal delivery route?

• Relatively reproducible absorption

• Low enzymatic activity

• Partial avoidance of 1st pass metabolism

What is rectal drug administration useful for drugs that?

• Undergo high hepatic first-pass metabolism

• Limited absorption in the upper GI tract

• Readily degradable or unstable in the GI tract

• Irritation to the gastric mucosa

• Cannot be easily formulated for other routes of administration

• Localized actions in rectum or distal colon

What are the 4 groups of suppository bases?

1. Fat- or oil-type base

2. Glycerin-gelatin base

3. Water-soluble or water-miscible polymers & surface-active agents

4. Bases containing disintegrating agents

What are the 6 general classes of suppository bases?

• Cocoa butter

• Cocoa butter substitutes

• Glycerinated gelatin

• Polyethylene glycol base

• Surfactant base

• Tableted suppositories or inserts

What are the desired properties for the formulation & preparation for suppository bases?

• Releases easily from suppository molds

• Non binding of drugs

• Mixes w/ or absorbs some water

• Viscosity low enough when melted to pour easily but high enough to suspend particles of solid drug

• Some wetting &/or emulsifying properties so that it will spread, disperse in, & release active ingredients at administration site

What are the properties of Cocoa Butter NF?

• Solid at room temperature

• Melts at body temperature

• Melting point of 31-34C

• Does not absorb significant amounts of water

What is the solubility of Cocoa butter NF?

• Insoluble in water

• Slightly soluble in alcohol

• Soluble in boiling absolute alcohol

What are the advantages to cocoa butter NF?

• Nonirritating

• Excellent emollient

• Can be used for hand-molding suppositories

• Solidification temperature 12-13 below its melting point, so it is easy to pour suppositories before the base solidifies

What are the disadvantages to cocoa butter NF?

• Exists in several polymorphic forms that have even lower melting points: 18, 24, & 28-31C

• Poor & somewhat erratic release of some drugs

What is cocoa butter both?

Excipient & active ingredient

What is Witepsol?

• Cocoa butter substitute

• Contains emulsifying agent

• Will absorb small amount of water

What is fattibase?

• Cocoa butter substitute

• Includes self-emulsifying glyceryl monostearate & polyoxyl steerage, which serve as emulsifier & suspending agents

• Suppositories should be poured when mixture 43-49%

• Made from this base release well from molds

How to choose the right base?

1. Patient comfort

2. Compatibility & stability

3. Local effects

4. Systemic effects

• From fatty bases drug release is driven by partitioning

• Poor drug release/bioavailability from fatty bases

• Surfactants in the base (fattibase) may improve drug release/bioavailability

What are the different kinds of molds?

• Aluminum metal molds

• Plastic suppository shells

• Flexible rubber molds

• Very hard rubber molds