Pharmaceutics II – Rectal Drug Delivery

rectal drug delivery formulations:

- rectal suppository

- rectal rocket

- rectal enema

- rectal foam

- rectal gel, cream, ointment

rectal suppository

- various sizes/shapes

rectal foam

- easy to retain

- provides better coverage

rectal gels, creams, ointments

- require applicator

- can be used externally

rectal rocket

- designed to get drug to the site of action

- holds drug at site of action for extended period

- available only as compounded product

Rectal rockets are used for...

hemorrhoids

advantages of rectal rockets:

- does not get lost, remains at point of application/insertion

- treats both internal/external hemorrhoids

- patient can expel gas without losing suppository

rectal vasculature

- highly vascular

- avoids first pass metabolism

- may result in erratic drug absorption

advantages of rectal drug delivery:

- minimize effects of first pass metabolism

- avoid problems of GI administration

- suitable for patients unable to swallow

- provide local action

disadvantages of rectal drug delivery:

- poor patient acceptance

- erratic drug absorption

- not suitable for large volumes or drugs that irritate the rectum (unless it's for laxatives)

What bodily components can affect rectal drug absorption?

- variable blood flow

- rectal mucosal and disease conditions

- rectal content

factors influencing rectal drug absorption:

- placement and retention of dosage form

- mechanism and rate of drug release

- rectal content, disease conditions

- physiochemical properties of drugs/excipients

types of suppository bases:

- fatty (oleaginous)

- water soluble/miscible

fatty (oleaginous) bases:

- cocoa butter (theobroma oil)

- synthetic triglycerides (hydrogenated vegetable oils)

water soluble/miscible bases:

- glycerinated gelatin

- mixtures of PEGs

- fatty acid esters of PEGs

Diazepam rectal gel:

- lipophilic drug

- rapid onset of action required to treat seizures

desirable properties of suppository bases:

- either melts or dissolves in rectal fluid

- solid at room temp.

- non-irritating to rectal mucosa

- should provide suitable drug release profile

Rectal Drug Delivery - Local Effects Examples

- laxatives

- colitis

- hemorrhoids/anal pruritus

- anal fissure

- diagnostic aid

laxative examples:

- bisacodyl, lactulose, glycerin

colitis examples:

- mesalamine, budesonide, hydrocortisone

hemorrhoids/anal pruritus examples:

- hydrocortisone, pramoxine, phenylephrine

anal fissure example:

nitroglycerin

diagnostic aid example:

barium, iohexol, diatrizoate

Rectal Drug Delivery - Systemic Effects

- analgesic

- antiemetic

- antimigraine

- anticonvulsant (seizures)

analgesics example:

hydromorphone, APAP, indomethacin

antiemetic example:

prochlorperazine, promethazine

antimigraine example:

ergotamine, caffeine

anticonvulsant (seizure) examples:

diazepam

hyperkalemia example:

sodium polystyrene sulfonate

treatment for hyperkalemia from sodium polystyrene sulfonate:

- administer cleansing enema

- irrigate colon at the end to remove resin

5-aminosalicylic acid derivatives:

- Dipentum

- Balsalzide disodium

- Azulfidine

- Azulfidine EN-tabs

Example of Suppository:

Migergot

Migergot

- treatment and prevention of migraine

- beneficial for patients with excessive nausea or vomiting symptoms

Migergot Storage Conditions:

- below 77˚F and in tight container

- sealed foil that maintains shape

Suppository Steps:

1. wash hands

2. remove suppository from packet

3. lie on side with one leg bent and the other straight

4. gently insert into rectum

5. lower legs and lie/sit for a few minutes

6. wash hands again

7. try not to empty bowels for at least an hour (unless the suppository is a laxative)

rectal enemas:

- solutions or suspensions

- administered into rectum

uses of rectal enemas:

- cleansing or evacuation

- provides local drug effect

example of rectal enema:

Rowasa rectal suspension

positions for rectal enemas:

- left-side position

- knee-chest position

Barium Enema:

diagnostic aid for computed tomography or x-ray examinations of GI tract

Rectal Foam Examples:

- Cortifoam

- Uceris

advantages of rectal foams:

- spreads well in rectum

- provides uniform coverage, retained in rectum better

- used for treatment of UC of rectum

- good for patients who cannot retain enemas

Uceris

- induction of remission in patients with active, mild to moderate distal UC

rectal foam excipients:

- foaming agents, surfactants/emulsifiers

- solvents

- propellant

- preservatives, antioxidants

rectal foams excipients - foaming agents, surfactants/emulsifiers

- stabilize air-water interface of foam (bubbles)

- polyoxyl stearyl ether, emulsifying wax, fatty alcohols

rectal foam excipients - solvents

- propylene glycol, water

rectal foam excipients - propellant

- n-butane, isobutane, propane

- delivers medication

rectal gels example:

diazepam rectal gel

diazepam rectal gel

- for status epilepticus and breakthrough seizures

- easy to administer during emergency (rapid onset)

rectal gel inactive ingredients:

- propylene glycol, ethyl alcohol

- hydroxypropyl methylcellulose

- sodium benzoate, benzyl alcohol

- benzoic acid, water

rectal ointment example:

Rectiv

Rectiv

- moderate to severe pain associated with chronic anal fissure

- improve blood flow and reduce muscle tension

Rectiv inactive ingredients:

- propylene glycol, lanolin

- sorbitan sesquioleate

- paraffin wax, white petrolatum

rectal cream example:

Hydrocortisone 1%

Hydrocortisone rectal cream:

- reduces inflammation

- treats itching or swelling caused hemorrhoids or idiopathic external anal pruritus

- may require applicatory syringe