Rectal and Vaginal Drug Delivery

Rectum - site of administration:

• ~15cm straight portion of the large intestine

• ~3mm thick of simple columnar epithelium (less permeable than SI)

• ~300 cm² area

• of rectal fluid 1-3 ml at pH 6-7

• drugs absorbed into the rectal veins via diffusion and 1st pass-hepatic metabolic loss is avoided for systemic delivery

Vagina - site of administration:

• 6-10 cm long, thin-walled, muscular tube

• non-keratinized, stratified squamous epithelium

• 60-100cm² area

• 0.5-2 ml at pH 3-4; no buffer capacity

• drugs are absorbed into the vaginal veins via diffusion

• 1st pass hepatic metabolic loss is avoided for systemic delivery

What are the rectal/vaginal dosage forms?

• suppository

• tablet (capsule)

• ointment, cream (aerosol foam)

• gel, film

• vaginal ring, (sponge)

• intrauterine device (IUD)

• solution and suspension

• powders for solution

What are the local acting rectal drugs?

• glycerin

• bisacodyl

• hydrocortisone

• mesalamine

• benzocaine

• pramoxine

What are the systemic acting rectal drugs?

• ASA

• APAP

• ibuprofen

• indomethacin

• oxymorphone

• diazepame

• cholorpromazine

• promethazine

What are the local acting vaginal drugs?

• anti-infectives

• spermicides

• contraceptive and estrogenic hormones

What are the systemic acting vaginal drugs?

• estrogenic hormones

What are the advantages of rectal dosage forms?

• bioavailability is higher for drugs usually degraded by GI and 1st pass

• more suitable for pediatric, geriatric, or terminally ill (also N/V)

• onset and duration of drug action is controlled by selecting appropriate base

What are the disadvantages of rectal dosage forms?

• poor patient acceptance/adherence

• absorption is slower than oral

What is a suppository?

• drug/base mixture molded into shape

• base melts at body temp to release drug

• individually wrapped in foil or PVC-PE

• stored at 20-25C or in fridge

What bases are there for suppositories?

• fatty/oleaginous base: cocoa butter, glycerin w/ high MW fatty acid

• water-miscible/soluble base: glycerinated gelatin, polyethylene glycol (PEG)

The drug release rate depends on the drug’s ____________ from formulation into the rectal or vaginal mucosa.

escaping tendency

Lipophilic drugs for systemic delivery - base choice:

• oleaginous bases don’t release well

• water-miscible bases can release the drug quickly, enabling faster absorption

Hydrophilic drugs for local delivery - base choice:

• oleaginous bases can release the drug quickly enabling rapid location action

• water-miscible bases release the drug, but the rate is slower than that from oleaginous bases

What is the PK of rectal suppository Methadone?

• lipophilic drug, the water-miscible base allows faster and greater absorption compared to the oleaginous base

What is the PK of rectal suppository Oxymorphone?

• water-miscible base provides immediate release of hydrophilic drug (oily base would be too fast)

• creates an IM-like pain relief profile but done so without an inj.

• 50% bioavailability (10% higher than oral) b/c 1st pass is avoided

Antifungals or bacterials in vaginal suppository are for ____ actions only.

local

Most vaginal suppositories are _____ and _____ with devices or applicators.

PEG-based; self-administered

What are vaginal suppository formulations buffered to?

• 3-4 pH

• matches vaginal fluid acidity and contains preservatives

Vaginal cream and tablet:

• estrogenic hormones for local post-meopausal vulvar and vaginal atrophy

• self-administration w/ applicators

• lipophilic drugs are formulated in water-miscible creams and film coated fast disintegrating tablets

• daily application necessary as release isn’t sustained

Vaginal film - contraceptive:

• spermicide formulated in an instantly dissolving thin polymer film

• OTC local contraceptive on contact

• effective 15mins -3 hr after application

• purpose is not systemic absorption or an inc. in blood levels

Vaginal ring - contraceptive:

• etonogestrel and ethinyl estradiol (EE) formulated in a non-biodegradable polymer ring

• polymer-based matrix-type Er over 21 days for local and systemic actions

• EE dose is lower than the oral pill, maintains blood levels just above the trough level of oral pills

• non-sterile application by patients

Vaginal rings for post-menopause:

• polymer-based matrix-type ER over 3 months

• Femring for systemic/local

• Estring for local

• also differ in dosage and delivery rate

Intrauterine devices (IUDs):

• silicone-based T shape (3×3 cm) local contraceptives for 3-10 years

• LNG (levonorgestrel) is absorbed from uterus however, blood levels are lower than those with oral pills

• sterile products applied by clinicians

• most effective, equivalent to implants