ceutics suppositories

identify reasons as to why suppositories may be used over oral routes

- unable to take orally (oral surgery, throat pain)

- not available in parenteral form/ scared of needles

- gastrectomy/ unable to absorb

which regions of the body are suppositories intended for

rectal, vaginal, urethral

which suppository can have systemic effects? why?

rectal- has hemorrhoidal veins that allow drug to reach circulation (as opposed to vaginal and urethral)

3 hemorrhoidal veins

1. superior hemorrhoidal vein

2. middle hemorrhoidal vein= where most drugs absorbed

3. inferior hemorrhoidal vein

- allow for systemic absorption of rectal suppositories

what allows for systemic absorption of rectal suppositories

mainly middle hemorrhoidal vein

hemorrhoids

Swollen, painful rectal veins; often a result of constipation

characteristics of an ideal suppository base

-must be firm enough to insert at RT

- must melt (oleaginous)/ dissolve (water soluble) at 37C, and not leak out

- nonirritating

- stable during manufacture & storage

- chemically compatible with drug

rectal suppository usually have ______ bases, while vaginal/urethral have _________

rectal= oleaginous/cocoa butter (residues passes w stool)

vaginal/urethral= water soluble/dispersible (not as irritating)

cocoa butter (aka ______________) is a mixture of

theobroma oil

mix of: POLLS

Palmitin

Olein

Laurin

Linolein

Stearin

-> and other long chain fatty acid glycerides

how can theobroma oil be extracted

soluble in ether and chloroform; may be extracted via separation

limitations of cocoa butter in suppositories

- unsuitable for vaginal and urethra (irritating)

- hydrophobic

- mp lowers after drug incorporation (think of crystal point lowering when theres contaminants)

- polymorphic= multiple crystalline forms

Examples of cocoa butter substitutes (synthetics)

- witepsol

- wecobee

(long chain fatty acids that are synthesized)

types of water soluble bases for suppositories

PEG, glycerinated gelatin, surfactant

t/f: oleaginous bases are slower to soften, having slower release and onset

false. water soluble bases are slower to soften and mix with physiological fluids= slower release

- think of butter vs jello melting. jello takes longer

a suppository is made up of PEG 4000. describe the characteristics of it

-water soluble suppository base

-will take longer to soften, having slower release

-better for urethral/vaginal use than oleaginous bases

3 ways to prepare suppositories

1. hand rolling/ shaping

2. compression

3. fusion/ melt molding

describe the compression method for suppository formation

- can use cocoa butter or PEG base

- can use heat sensitive drugs since this method does NOT involve heat (just mixing and compressing)

- suitable for drugs that are insoluble in the base (bc just mixing)

describe the fusion/molding method for suppository formation

- can use cocoa butter, PEG, or glycerinated gelatin

- can NOT use heat sensitive drugs since you melt this

- can NOT use insoluble powders

factors to consider when choosing suppository bases

SCAR

1. solubility of drug in bases

2. compatibility of drug w base

3. application site (no cocoa butter for vaginal/urethra)

4. rate of drug release/ absorption

if a suppository is formulated with a lipophilic drug in cocoa butter, is the release rate going to be faster or slower

slower. "like dissolves like", since both are lipophilic, it will take longer for drug to leave base

rank rectal, vaginal, and urethral suppositories base on size

smallest-> urethral, rectal (1-2g), vaginal (5g)

compressed tablets, soft gelatin capsules, and urethral inserts may be used as suppositories but may cause

irritation/ inflammation. not rlly recommended unless theres a need

what could cause a fail in treatment of a urethral insert

peeing after urination (not enough time to release/ treat area)

(for rectal, may be covered by feces)

advantages of suppositories

1. avoid oral/ parenteral route (ex: oral surgeries)

2. localized site of action (ex: hemorrhoids, infection)

disadvantages of suppositories

1. inconvenience (ex: melt, deep)

2. unpredictable absorption (ex: did it dissolve/ reach circulation? covered by mucus/ feces?)

3. mucosal irritation

4. high cost

how deep should a rectal suppository be inserted

must be inserted deep enough to get past anal sphincter

- middle hemorrhoidal vein is on interior of anal sphincter

a pt inserted a rectal suppository and could not fight the urge to defecate. how will this affect drug pharmacokinetics

will not be in therapeutic range/ not enough time for release