PHARM 125 - Rectal and Vaginal Dosage Forms

Vaginal inserts are also called:

Pessaries

Urethral inserts are also called:

Bougies

True or false: suppositories are less irritating to the GI tract.

Yes, this is an advantage of suppositories

Are suppositories intended for local or systemic effect?

Can be both.

True or false: suppositories avoid the first-pass metabolism

True-ish, they can if administered correctly.

True or false: poor compliance is associated with suppositories.

True, this is a disadvantage

True or false: some suppositories can cause irritation of mucous membranes.

True

What is the shape of a rectal suppository?

Bullet or torpedo shape

What is the weight of a baby, adult, and rectal rocket suppository?

Baby = 1g

Adult = 2g

Rectal rocket = 4-5g

What is the shape of a vaginal suppository?

Usually globular, oval, or cone-shaped

What is the weight of a vaginal suppository?

~3-5g

What kind of vehicles are vaginal suppositories usually made from?

Water-soluble or water-miscible vehicles such as polyethylene glycol or glycerinated gelatin

In which type of suppository would you find nonoxynol-9?

Vaginal suppository (contraceptive due to spermicidal properties)

What is the weight of a female urethral suppository? Male urethral suppository?

~2g

~4g

What is the diameter of urethral suppositories?

3-6mm

What is the length of a female urethral suppository?

25-70mm

What is the length of a male urethral suppository?

50-125mm

In which type of suppository might you find Alprostadil?

Urethral suppository (used for erectile dysfunction)

The composition of suppositories can be broken down into these three categories:

1. Active ingredients

2. Additives

3. Suppository bases

What kind of active ingredient would framycetin be?

Antibacterial

What kind of active ingredient would bismuth subgallate be?

Astringent

Would suppository antifungals be used for local or systemic action?

Local

Would antibacterial suppositories be used for local or systemic action?

Local

Would astringent suppositories be used for local or systemic action?

Local

Would anti-emetic suppositories be used for local or systemic action?

Systemic

Cetyl alcohol and propylene glycol are what kind of additive?

Plasticizers (givers flexibility)

_______ are additives to suppositories which are used to improve flexibility

Plasticizers

What kind of additive is butylated hydroxytoluene (BHT)?

Antioxidant

________ are additives to suppositories which protect the drugs and bases from getting degraded by oxidation

Antioxidants

What kind of additive is silicon dioxide?

Viscosity enhancer (suspending agent)

________ are additives to suppositories that increase wetting and spreading and may increase permeability of the rectal mucosal membrane

Absorption enhancers (surfactants)

True or false: surfactant can be used as dispersants in suppositories.

True

True or false: an ideal suppository base should be non-absorbable.

True

What kind of suppository base is Witepsol?

Fat/oleaginous/hydrophobic

What kind of suppository base is Fattibase?

Fat/oleaginous/hydrophobic

What kind of suppository base is glycerin-gelatin?

Hydrophilic/water-soluble

What kind of suppository base is PEG?

Hydrophilic/water-soluble

What kind of suppository base is Polybase?

Hydrophilic/water-soluble

What kind of suppository base is polyoxyl 40 stearate?

Hydrophilic/water-soluble

Another name for theobroma oil is?

Cocoa butter

Cocoa butter is a mixture of the glyceryl esters of ______, _______, _______, and other fatty acids.

Stearic, palmitic, oleic

True or false: cocoa butter is compatible with many ingredients.

True

True or false: cocoa butter is prone to polymorphism.

True, depending on how slowly it is cooled down after being melted

What is the melting point of the alpha polymorph of cocoa butter?

~22 degrees Celsius

What is the melting point of the beta polymorph of cocoa butter?

~35 degrees Celsius

What is the most stable polymorph form of cocoa butter?

Beta polymorph (MP ~35 degrees Celsius)

How are semi-synthetic fatty bases made?

By hydrolyzing vegetable oil + hydrogenation, and re-esterifying the acids by heating with glycerol

True of false: semi-synthetic fatty bases can experience polymorphism

False, they are easier to work with

True or false: semi-synthetic fatty bases should be stored in the fridge

True

Semi-synthetic fatty bases may be more irritating that cocoa butter because they can have a _______ effect.

Dehydrating

What is the composition of glycerol-gelatin base?

A mixture of glycerol and water made into a stuff jelly by adding 20% gelatin

True or false: glycerol-gelatin bases will melt at body temperature.

False, they will rather slowly dissolve in the secretion of the mucous lining of the rectum and vagina

Glycerol-gelatin bases are used frequently for _______ suppositories.

Vaginal

Which base would be better as an antiseptic, glycerol-gelatin or fatty bases?

Glycerol-gelatin, dissolves slowly in about 30-40 minutes

What kind of physiological action do glycerol-gelatin bases have?

Glycerol suppositories are laxatives

True or false: glycerol-gelatin bases are hygroscopic.

True, they require careful storage

Since glycerol-gelatin bases are hygroscopic, what effect does this have on the mucosa?

It can cause dehydration and irritation of the mucosa

What does PEG stand for?

Polyethylene glycol

Do PEG base suppositories require refrigerator storage?

No, mixtures have melting points above 42 degrees Celsius

True or false: PEG suppositories melt at body temperature.

False (MP too high), instead, they gradually dissolve and disperse in the fluids

Which base has a more prolonged release of drug, cocoa butter or PEG?

PEG because it takes 30-50 minutes to dissolve (it does not melt at body temperature)

How can physical properties and melting points be adjusted for PEG bases?

By varying the mixture of high and low molecular weight polymers

Will a PEG base leak from the body?

No

PEG bases are ______, meaning they absorb moisture from their environment.

Hygroscopic

(this can cause irritation of rectum)

Why would a PEG base suppository be moistened with water before insertion?

Because it has a hygroscopic nature which could cause irritation to the rectal mucosa

True or false: PEG base will not contract significantly on cooling.

False, it will (formation of pits/holes)

PEG bases are incompatible with _______ substances (ex. tannic acid, aspirin, benzocaine, salicylic acid)

Phenolic

Why should you not put aspirin in a PEG base?

Because PEG bases are not compatible with phenolic substances

Why should you not put tannic acid in a PEG base?

Because PEG bases are not compatible with phenolic substances

Why should you not put benzocaine in a PEG base?

Because PEG bases are not compatible with phenolic substances

Why should you not put salicylic acid in a PEG base?

Because PEG bases are not compatible with phenolic substances

Does fluid in the rectal cavity have any buffer capacity?

No

The ______ rectal veins transport drug to upper part of the rectal cavity the liver

Superior

The _____ rectal veins transport drug into inferior vena cava and bypass the liver

Inferior

You should add a suppository to the ____ part of the rectum if you want to bypass the liver.

Lower

____ drugs will have a good release from oleaginous-based suppositories, resulting in absorption.

Hydrophilic

______ drugs tend to remain in oleaginous bases and lead to little absorption.

Lipophilic

If possible, the ________ form of a lipophilic drug should be used in an oleaginous base.

Ionized salt (so that it can exit the oleaginous base)

PEG bases with _______ MWs will have longer dissolution time.

Higher

Preparation of suppositories:

________ is a historic part of the art of the pharmacist.

Hand-rolling and shaping

Hand-rolling and shaping is usually done with ______ because it is easy to manipulate.

Cocoa butter

When could you use compression molding to make a suppository?

- Heat-labile substances

- Substances that are insoluble in base

True or false: compression molding is usually done by hand.

False, it requires a special suppository machine (disadvantage)

Which method of suppository preparation did we use in lab?

Fusion molding

True or false: hygroscopic products like glycerol suppository should be wrapped in grease-proof paper.

False, they should be dispensed in well closed glass or plastic containers

We need to account for the density of the drug if there is more than _____mg of the drug in the suppository.

100

What is the density factor?

How much of a drug is necessary to displace 1g of base

You need to prepare 12 suppositories containing 180mg of tannic acid. Tannic acid has a DF in cocoa butter of 1.6. (mold calibration = 2g). How much will each suppository weigh?

~2.06g

Calculate the quantities of base and drug requires to prepare 6 suppositories weighing 1g, each containing 250mg of bismuth subgallate (density factor = 2.7, mold calibration = 0.94g), make 2 extra.

Base = 6.78g

Drug = 2g

If 200mg of aspirin is to be incorporated into each PEG suppository; how much PEG base will be displaced by aspirin? (DF of aspirin in cocoa butter is 1.3, PEG/cocoa butter ratio is 1.2)

0.185g of PEG base will be displaced

What is the estimated density factor?

It is estimated that powders have an average displacement of 0.7g of suppository base for each gram of drug

When do we use the double casting method?

When the density factor is not known

What formula is used for the Paddock Method (double casting)?

DF =B/[(A-C) + B]

A = blank average weight

B = weight of API per suppository

C = average weight of a medicated suppository

You need to prepare 8 fatty base suppositories containing 350mg of drug. Black weight is 1.9g and average weight of the medicated suppository is 2.1g. What is the density factor?

DF = 35/[(1.9-2.1)+0.35]

= 2.3

Prepare 8 PEG suppositories in a 2g mold that contains 1% of hydrocortisone. The blank suppository weighs 1.9g.

1.9g x 8 = 15.2g

15.2g(1/100) = 0.152g

Weight of base required = 15.2-0.152 = 15.05g