L4 - Suppositories

What is a suppository?

Solid dosage for intended for insertion into body orifices

Where is the drug found in a suppository?

It is incorporated into the base

How do suppositories work?

They melt, soften, or dissolve at body temperature

What percentage of drug products are suppositories?

<0.0005%

T/F: Suppositories are always medicated?

False, they can be either medicated or unmedicated

What are the three routes of administration for suppositories?

- Rectal

- Vaginal

- Urethral

What is the usual weight of a rectal suppository and what is the base?

About 2g of cocoa butter suppository

Are children and infant suppositories the same weight as adults?

No, they are about half the weight of an adult suppository

Do rectal suppositories have a local or systemic effects?

They have both local and systemic

2 multiple choice options

What else are urethral suppositories also known as?

Bougies

What are urethral suppositories made of?

waxed linen, gelatin, plastic, rubber, or even metal

What applications do urethral suppositories have?

Local and urological

What is another name for vaginal suppositories?

Pessaries

What are the different shapes of vaginal suppositories?

Globular, oval, cone, tablet shaped

What is the usual weight of a vaginal suppository?

About 5g cocoa butter pessary

What are vaginal pessaries used for?

-Combat local infections

-Contraception

-Restore the vaginal mucosa to its normal state

-Pregnancy

-Menopause

-Discomfort due to pelvic organ prolapse

What are some of the advantages of rectal route?

-No enzymatic or pH degradation

-Limited first pass effect

- Irritating drugs

- Taste does not matter

-Used if patients aren't able to or are unwilling to swallow meds

-Used when patients have nausea, vomiting or stomach surgery

- Used for unconscious patients

- Usually good for children or the elderly

What are the disadvantages of rectal route?

-Inter and intra subject to variation (inconsistency on how the drug is absorbed through the rectum)

-Slow and incomplete absorption

-Special storage requirement

What would be the local effects that a rectal suppository has?

-Hemorrhoids or other anorectal conditions

-Anusol suppositories

-Glycerin suppositories (laxative)

What would be the local effects that a vaginal suppository has?

-contraceptives

-antiseptic

-restoring environment

What would be the local effects that a urethral suppository has?

-Antibacterial

-local anesthetic fro urethral examination

What would be the systemic effects that a vaginal suppository has?

hormones

For systemic effects what is more frequently used, rectal or vaginal?

Rectal route

Do urethral suppositories have systemic effects?

No

Can urethral suppositories be used for erectile dysfunction?

Yes

Is the dose for rectal suppositories large or small?

large, up to 1 g

Is the dose for vaginal suppositories large or small?

Moderate dose, up to 200 mg

Is the dose for urethral suppositories large or small?

Low dose, up to 1 mg

Do recital suppositories have a applicator?

No, only vaginal and urethral

When will you see more systemic absorption fro a rectal suppository?

When the colon is empty

What are the rectal conditions necessary for drug absorption?

- rectum 10-15cm long

- 1 to 3 ml of mucous fluid

-immotile

-without villi or microvilli

-abundant blood and lymphatic vessels

How is first pass avoided through the rectal route?

if absorbed through the hemorrhoidal veins at the lower part of the rectum.

For rectal suppositories can first pass happen?

Yes, if the suppository is inserted higher

Where can absorption occur through where as well?

Lymphatic circulation

What is the nature of the base?

-Melting, softening, or dissolving

-MP should not be higher than 37 degrees C

-an irritant of the mucous membrane

Are bases compatible with any medication or excipient?

Yes

What are the different classifications of suppository bases?

-Oleaginous/fatty

-Hydrophobic bases

-Miscellaneous

What is oleaginous/fatty bases?

-Melt in the rectum

-Cocoa butter

-Hydrogenated fatty acids of vegetable oils

-Glyceryl monosterarate, glyceryl monopalmitate

-Typically used for rectal suppositries

What does cocoa butter base contain?

contains triglycerides of oleopalmitostearin, oleodipalmito and oleodisterarin

What percentage of cocoa butter base fatty acid content is unsaturated?

About 40%

What is the melting range for cocoa butter?

30-36 degrees Celsius

T/F: cocoa butter exbhibits polymorphism?

True

What form is stable for cocoa butter?

beta form, and tempering is down to maximize beta form formation. Transition back to beta form takes several days

What can lower the melting point of cocoa butter to below room temp?

phenol, chloral hydrate

What are two types of solidigying agents?

cetly esters wax and beeswax

Is cocoa butter only used for rectal suppositories?

Yes, NOT used for vaginal or urethral

Are cocoa butter suppositories elastic?

Yes

What are limitations to oleaginous/fatty bases?

-Polymorphism

-Adhere to the mold

-MP too low for hot climates

-Rancidity/degradation in storage

-Immiscible with body fluids

-Leakage

-Expensive

What is fattibase?

Triglycerides from palm, palm kernel and coconut oils, it is another fatty base

What is Wecobee?

Triglycerides from coconut oil

What Witepsol?

Triglycerides of saturated fatty acids

What are the advantages of oleaginous/fatty bases?

-Solidification unaffected by overheating

-Have a good resistance to oxidation

-Small difference between melting and setting points

-Risk of sedimentation of suspended ingredients is low

-Available in various grades

-Contains surfactant or w/o emulsifying agents

-No need to lubricate

-Less expensive

What are the disadvantages of oleaginous/fatty base?

-brittle

-low viscosity

What are hydrophilic bases?

-Water soluble or water miscible bases

-Dissolve or soften in body cavities

-Bases of choice for pessaries and bougies

-Glycerinated gelatin and PEGs

-Hydrogels, crossed-linked forms of PVA, hydroxyethyl methacrylate, polyacrylic acid, polyoxyethylene

What are the percentages of gelatin, glycerin, and drug following USP standards?

Gelatin 20%, glycerin 70% and water/solution or suspension of drug 10%

What are the percentages of gelatin, glycerin, and drug following BP standards?

Gelatin 14%, glycerin 70% and water/solution or suspension of drug 16%

What are the percentages of gelatin, glycerin, and drug for urethral suppositories?

60% of gelatin, 20% glycerin, and 20% of aqueous mixture of the drug

What type of suppositories mostly use glycerinated gelatin?

vaginal

T/F:Suppositories that are made with glycerinated gelatin are moisten with water prior to use?

True

1 multiple choice option

What are the disadvantages of glycerinated gelatin?

- Osmotic/laxative effect

-Erratic drug release

- Dehydrating effects on the mucosa

-Hygroscopic

-Microbial contamination

-Long preparation time

-Lubrication of the mold is essential

What are polyethylene glycols?

-Polymers of ethylene oxide

-Hardeness increases and solubility decreases with teh increase in molecular weight

-Two or more PEGS can be mixed by fusion to achieve a base with desired consistency

-Dissolve slowly

What are the advantages of hydrophilic bases?

-No leakage

-Stable

-Dissolve/disperse

-No lubrication

-No refrigeration

What are the disadvantages of hydrophilic bases?

-Irritation

-Hygroscopic

-Crystal growth

What are miscellaneous bases?

-Chemical or physical mixtures of oleaginous and hydrophilic bases

-Preformed w/o emulsions or materials capable of dispersing in aqueous fluids

-Mixtures of fatty bases with emusyfiying agents capable of forming w/o emulsions

What is an example of a miscellaneous base?

Polyoxyl 40 stearate

Look at table on slide 26 of powepoint

26 :0

What are some exipents used for suppositories?

- hydrophilic agent- starch

-colloidal silicon oxide or aluminum monosterate

-lecithin

-surfactants act as wetting/deagglomerating agents

-preservatives

-antioxidants

T/F: Colloidal silicon oxide or aluminum monosterarate are both approximately 1-2%?

True

What is the most popular molding method for suppositories?

Fusion molding

What is the process of fusion molding?

-Melting the base

-Adding the drugs

-Pouring the melt into lubricated molds

-Allowing the melt to cool and congeal

-Removing the suppositories from the mold

What are fusion molding molds made of?

stainless steel, aluminum, brass, and plastic

What bases can be used for fusion molding?

most bases

What is compression?

A method of suppository making where you force the base-drug mixture into special molds using suppository making machines

What are the advantages of compression?

-Thermolabile

-Insoluble

-polymorphism

What are the disadvantages of compression?

Needs special equipment, cannot form/ prepare all shapes of suppository

How are suppositories usually packaged?

In tin or aluminum, paper or plastic

What can poor packaging do to suppositories?

may give rise to staining, breakage or deformation by melting

Which type of suppositories are stored preferably in a fridge?

cocoa butter and glycerinated gelatin suppositories

Which suppositories are usually stored at usual room temperature?

Polyethylene glycol

What are quality issues seen with suppositories?

-unpleasant odor

-shape deformation

-whitening on the surface

-other aging phenomena, such as Harding, softening, bloom, moltting, discoloration, and cracking may occur over time

Look at slide 33 on the powerpoint

33 :)

What are some patient counseling tips?

-Wash your hands thoroughly with soap and then dry.

-Place the suppository in a refrigerator for a few minutes if it is soft.

-Remove the wrapper.

-If it was instructed to use half of the suppository, the

suppository should be cut lengthwise with a clean, single-edge razor blade.

- Put on a finger cot or disposable glove, if desired.

-Lubricate the suppository with a water-soluble lubricant (e.g., K-Y® Jelly). If lubricant not available, moist the rectal area.

counseling tips continued...

-Lie on your left side with your lower leg straightened out. Bend your right knee up forward toward your stomach.

-Lift upper buttock to expose the rectal area.

-Insert the suppository, pointed end first, with your finger until it passes the muscular sphincter of the rectum, about ½ to 1 inch in infants and 1 inch in adults

-Hold buttock together for few seconds.

-Remain lying down for about 5 min.

-Wash your hands thoroughly.

What are more patient counseling points?

- Inform patient that it is not for oral use

-Use language the patient can understand

-Unwrap before the suppositories before inserting