Vaginal delivery

Question 1

What is vaginal drug delivery used for?

Answer 1

less common than rectal drug delivery

local actions
- anti-infectives = miconazole, clindamycin
- spermicides 
= contraceptive
= nonoxynol-9
- microbicides 
= prevent transmission of STD = HIV viruses
= not approved yet

systemic actions

• higher bioavailability compared to oral administration = avoid first pass completely
• progesterone, oestrogens = vaginal creams/ hydrogels

Question 2

What is the vagina?

Answer 2

vagina
- is a fibro-muscular tube that connects the uterus to the external environment

covered with cervico-vaginal fluid for protection and lubrication during sexual activity
- vaginal fluid contains microflora = lactobacillus

pH provides protection from infections and rise by local infections and at post-menopausal stage.

Question 3

How are drugs absorbed from the vagina?

Answer 3

vagina

• is well suited for drug absorption for systemic action
• contains vast network of blood vessels

drugs are drained by vaginal vein into the inferior vena cava
- avoids first pass effect completely = enter systemic circulation

Question 4

What are the advantages of vaginal delivery?

Answer 4

suitable when oral intake is restricted

avoids interaction with gastric content

avoids first pass metabolism completely = drained by
vaginal vein into the inferior vena cava

high vascularization

relatively large surface area for absorption

relative low enzymatic activity

uterine pass effect

• preferential delivery to uterus
• danazol and progesterone.

Question 5

What are the disadvantages of vaginal delivery?

Answer 5

is gender specific

drug absorption is affected by menstrual cycle and hormonal variations

leakage of dosage form

microbial infections will affect pH and drug stability and release

systemic absorption might occur for locally administered drugs.

Question 6

What are the different vaginal dosage forms?

Answer 6

liquids = solutions, emulsions and suspensions

semisolids = creams, gels, ointment

solids = pessaries, ring, films, tablets and capsules

gaseous =foams and sprays

Question 7

What are the features of the ideal vaginal dosage form?

Answer 7

should be long acting = reduce frequency of administration

stable in the vaginal fluid

should not lead to irritation, burning or itching

should not cause leakage

should be easy to insert

should not affect sexual activity.

Question 8

What is a pessary?

Answer 8

solid, single dose , usually ovoid in shape.

contain API, diluents, lubricants, antimicrobial preservatives, surface active agents

Glycerol-gelatin base = most common, well tolerated)
PEG = promote irritation

fatty excipients (synthetic Witepsol offer better stability than theobroma oil)

Question 9

What are vaginal rings?

Answer 9

circular systems that entrap the drug inside a polymer

silicone elastomer vaginal rings = polydimethylsiloxane

thermoplastic vaginal rings = poly(ethylene vinyl acetate)

control the drug release

Question 10

What are microbicides?

Answer 10

microbicides are creams, gels, films, or foams that can be inserted into the vagina or rectum to protect against STIs.

API is anti-retroviral drugs (25 available)

currently there are more than 10 microbicide formulas in clinical trials, including 1 product in a phase III trial.