Drug delivery to the vagina

What is the anatomy and physiology of the vagina?

S-shaped fibromuscular tube 6-10cm long

Connects the uterus to the external environment

What are the for layers of the vaginal wall?

Epithelial layer

lamina propria

muscular layer

tunica adventitious

What changes occur to vagina during menstruation cycle?

Thickness of epithelial cell layer changed by 200-300 micro meters

What is the surface of vagina covered in?

Covered in rugae which provides distensibility, support and an increased surface area

How is vaginal fluid produced?

Fluid arises from cervical secretion, transdudation from the blood vessels and secretion from the endotrium and fallopian tubes.

How much fluid do reproductive age and post menopausal women produce?

Reproductive - 3-4 g/h

Post menopausal - reduced by 50%

How is pH in vagina maintained?

Lactobacillus acidophilus present in vagina, produce lactic acid and maintain ph 3.8-4.2

This pH increases during menstruation and also during local infection and post menopausal

Why do we use vaginal drug delivery?

Used for both local and systemic effects but usually for local

Treatments for: infections, dryness, irritation, contraception, abortion, induction of layouts

Why do we use it for systemic?

sense network of blood vessels

drugs delivered via intravaginal may have better bioavailability as first pass metabolism is avoided

Suitable for patients where oral administration is not possible

possible to self administer and remove the dosage form

What are the challenges of vaginal drug delivery?

gender specific

local irritation

cultural sensitivity

leakage of dosage form

influence of sexual intercourse

variability in epithelium thickness, fluid and ph

What physiological changes occur in the vagina?

1 - cyclic changes in fluid volume may have either a negative or positive effect on drug absorption

2 - cyclic changes in pH and pH due to diseases or menopausal may change degree of ionization and alter absorption

3 - changes in the vaginal epithelium thickness impact absorption

How does menstrual cycle affect drug delivery?

Mucus secretion varies through the cycle, considerably increased by oestrogen during ovulation

vaginal ph increases during menstruation

luteal phase: fluid thin and less acidic. ovulation jelly like

How does pregnancy affect vaginal drug delivery?

The vaginal mucosa becomes thicker

Increase desquamation of the superficial vaginal mucosal cells with increased vaginal charge

How does age affect vaginal drug delivery?

Pre puberty - mucosal epithelium is thin

Vaginal ph around 5

Post menopause and after hysectomy oestrogen deficiency results in:

epidermis much thinner

reduced elasticity and vascularisation

reduced secretions

reduced glycogen ph can return to ph 7

patients more prone to dryness, irritation and infection

What are the indication for vaginal therapy?

1 - Infections and STISs

2- Induction of labout and abortion

3 - Spermicide

4 - Prevention of STD transmission

5 - Vaginal dryness

6 - Contraceptives

What considerations do we need to have in formulation design for vaginal drugs?

Must be non-irritant and non drying, cannot burn or itch

should be easy to insert or apply

should not cause leaking

should not stain or discolor undergarments

the formulation should not adversely affect sexual activity

women should be able to use it without the knowledge of a partners

should be compatible with vaginal environment

How big should the particle size be?

Not larger than 50 um as larger can cause mechanical irritation

How should the solubility of the drug be?

If the drug is highly lipophilic then water-soluble base preferred for release

if the drug is highly hydrophilic the lipid base preferred for release

What are vaginal suppositories (pessaries)?

Solid, single dose preparations for vaginal insertion

What are the challenges with vaginal suppositories?

Don’t want drug retained in base, so base needs to be opposite characteristic to drug so they partition out easy

What are the disadvantages of aqueous vehicles?

Hydroscopic and therefore attractive h2o which leads to a painful sensation

many incompatible drugs

drug release slow as drugs tend to stay in base

drugs may reduce melting point and viscosity of the base

surfactants will aid spreading but may irritate