L1 - Vaginal

Why is the vagina a favorable drug site?

Avoidance of first pass effect, rich vascularization, and low enzymatic activity

The vaginal cavity has potential for noninvasive, controlled transmucosal drug delivery for what effects?

Local and systemic

Local effects of vaginal delivery

Antifungal, steroids, antimicrobials, birth control, etc.

Systemic effects of vaginal delivery

Ovulation inducing activity, urogenital tract infections, hormone replacement therapy, etc.

The rate and extent of drug absorption after intravaginal administration depends on?

Vaginal physiology, age, stage in menstrual cycle, and formulation factors

Give four therapeutic applications of vaginal drug delivery

Contraceptives, treatment of AIDS and HIV, treatment of STDs, and vaginal infections

Give three advantages of vaginal drug delivery

Avoidance of first pass effect, minimal systemic side effects, and local targeting of reproductive organs

Give three disadvantages of vaginal drug delivery

Patient noncompliance, local irritation, and variability in drug absorption related to menstrual cycle, menopause, and pregnancy

What are two mechanisms for vaginal drug absorption?

Transcellular and paracellular

Transcellular permeation

Drugs move through epithelial cells to be absorbed

Paracellular permeation

Drugs move in between epithelial cells (tight junctions) to be absorbed

The dominant permeation pathway depends on the drugs:

physiochemical properties

What drugs dominantly use the paracellular pathway?

Hydrophilic drugs

What drugs dominantly use the transcellular pathway?

Lipophilic drugs

Describe three key factors affecting vaginal drug delivery

Physiological factors, physiochemical factors of API, and formulation factors

Physiochemical factors affecting vaginal drug delivery

pH is acidic (3.5-4.5), enzymes are present, cycle changes, and hormone changes

Name some enzymes that affect vaginal drug delivery

Amylases hydrolyze glycogen into simpler sugars and sustain bacterial population

Physiochemical factors of the API affecting vaginal drug delivery

Molecular size, weight, partition coefficient, extent of ionization, and chemical nature

Formulation factors affecting vaginal drug delivery

Viscosity, penetration enhancers, and muco/bioadhesive properties all increase contact time between vagina and formulation

Penetration enhancers

Capable of promoting absorption and penetration of drug through the vaginal mucosa

Give an example of penetration enhancers

Bile salts

Mucoadhesive agents

Permit close contact of formulation with the vaginal mucosa surface by promoting adherence

Give an example of mucoadhesive agents

Hyaluronic acid and cellulose derivatives

Bioadhesive agents (polymer)

Agents capable of delivering the API for an extended period at a predictable rate

Give an example of bioadhesive agents

Carbomers, polycarbophil, and Prochieve TM (HRT)

Give local vaginal drug delivery systems

Suppositories, douches, sprays, solutions, gels, creams, films, patches, and rings

Give systemic vaginal drug delivery systems

Tablets, capsules, injectable, and implants