Vaginal drug delivery
Vaginal epithelium is permeable to a wide range of substances, including steroids, prostaglandins, antibiotics, estrogens, and spermicidal agents.
Most steroids are readily absorbed by vaginal epithelium, leading to their higher bioavailability compared with their oral administration, because of a reduced first-pass metabolism.
For drugs with high membrane permeability, vaginal absorption is determined by permeability of the aqueous diffusion layer, whereas for drugs with low membrane permeability, such as testosterone and hydrocortisone, vaginal absorption is determined by membrane permeability.
Vaginal ointments and creams contain drugs such as anti-infectives, estrogenic hormone substrates, and contraceptive agents. Contraceptive creams contain spermicidal agents and are used just before intercourse.
The vagina is a fibro-muscular tube approximately 10 cm in length comprised of three distinct layers namely;
- an outer adventitial layer,
- a middle muscularis layer and
- An innermost mucosal layer
The vaginal rugae and micro-ridges on the epithelial cell surface permit the vagina to expand, allow the placement of vaginal formulations and increase the surface area of the vagina thus enhancing drug absorption.
The vagina has remarkable features in terms of vaginal secretion, pH, enzyme activity and micro-flora. These factors affect formulation spreading and retention as well as absorption and drug release in vagina.
The pH of the healthy female genital tract is acidic (pH 3.5–4.5) and is maintained within that range by bacterial conversion of glycogen from exfoliated epithelial cells to lactic acid.
Ideality of intra vaginal drug delivery system
- Component should melt at vaginal temperature i.e. at 36 °C,
- Intra-vaginal drug delivery device should be non-toxic and non irritating,
- It should not have any meta-stable form,
- The preparation should have wetting and emulsifying properties.
- It should have proper viscosity, so avoid the leakage of preparation from vagina (in case of semisolid dosage form),
- The preparation should have proper bioadhesive/muco-adhesive properties, so increase the contact time between the membrane and Preparation.
Advantages of intra vaginal drug delivery system
- Prolonged release,
- Minimal systemic side effects,
- An increase in bioavailability,
- Use of less total drug than an oral dose,
- First-pass metabolism can be avoided,
- Self medication is possible.
- Contact with digestive fluid is avoided and degradation of drug is minimized.
- Nausea, vomiting, emesis induced through oral administration is avoided.
- Quick onset of action.
- Gender specificity,
- Patient incompliance,
- Only a few drugs are administered by this route,
- Variability in drug absorption related with menstrual cycle, menopause and pregnancy,
- Influence with sexual intercourse.
- Personal hygiene.
- Some drugs are sensitive at vaginal pH