Drug delivery to the vagina

Vagina

S-shaped fibromuscular tube connecting cervix to external environment

Vaginal epithelium layers

Epithelium, lamina propria, muscular layer, tunica adventitia

Rugae

Folds in vaginal wall increasing surface area and flexibility

Vaginal fluid origin

Cervical secretions, blood transudate, uterine secretions

Normal vaginal pH

3.8–4.2 in reproductive-age women

Lactobacillus acidophilus

Bacteria producing lactic acid to maintain acidic pH

Advantages of vaginal delivery

Avoids first-pass metabolism and allows self-administration

First uterine pass effect

Preferential delivery of drug to the uterus

Challenges of vaginal delivery

Variable pH, fluid volume, irritation, leakage

Systemic vaginal absorption

Drug uptake via transcellular or paracellular pathways

Vaginal dosage forms

Rings, gels, pessaries, tablets, creams

Bioadhesive gel

Formulation that adheres to vaginal epithelium to prolong action

Pessary

Solid vaginal dosage form that melts or dissolves to release drug

Hydrophilic base

Water-miscible suppository base aiding release of lipophilic drugs

Hydrophobic base

Fatty base aiding release of ionised drugs

Formulation design consideration

Must be non-irritant, discreet, and compatible with vaginal environment