What are advantages to the vagina as a dosage route?
- Large surface area
- Dense vascularization
- Avoids first-pass metabolism
- Relatively high permeability to many drugs
- Opportunity for delivery systems that can continuously release drug for prolonged time periods
- Self-administration
- Systemic exposure reduced and potential systemic SE avoided
Is the vagina used more often for local or systemic products?
Local
What is the shape, length, and width of the vagina?
- S-shaped
- 2 cm wide
- 6-10 cm long
What is the mucosa of the vagina similar to?
Buccal mucosa
Is there fluid in the vagina?
Yes, a thin film of vaginal fluid
What is the pH of the vagina? How is this maintained?
- For women of reproductive age, pH = 3.5-4.5
- Maintained by lactobacilli producing lactic acid
- For women younger or older than reproductive age, pH is neutral to slightly basic
What can affect the pH of the vagina?
Infection
What is the surface area of the vagina?
50-60 cm^2
Vagina allows easy and rapid absorption of ______ drugs
Lipophilic
What determines absorption in the vagina? How can this be improved?
- Contact time w/ vagina
- Improved by adding bioadhesives gel or device like a vaginal ring
How do different types of drug get absorbed by the vagina?
- Lipophilic drugs cross by passive diffusion
- Hydrophilic and ionized substances of low MW are absorbed by paracellular route
What is the volume of fluid in the vagina? What does this mean for systemic absorption?
- 2-3 mL
- Dissolution may be a rate-limiting step for systemic absorption for drugs w/ poor water solubility
What can help if a drug has a poor dissolution rate in the vagina?
Formulate as a solution or gel instead of a suppository or tablet
Where do blood vessels of vagina drain? What does this mean for first-pass metabolism?
- Drain into inferior vena cava
- First-pass metabolism is avoided
Does vaginal fluid contain enzymes? What effect does this have?
- Yes
- Can deactivate some drugs before absorption can occur
What are some disadvantages to the vagina as a dosage route?
- pH of vaginal fluid and thickness of epithelium vary w/ a px age, menstruation and presence of infection –> may affect drug permeability and result in variable drug absorption; products for local use may be absorbed & cause systemic SE
- Some formulations may leak or slip out
- Irritation from drug or delivery system can occur
- Some px reluctance
What is the most common dose form for the vagina?
Suppository or tablet
What drugs are used in intra-vaginal rings?
- Contraceptives
- Hormones
- Anti-HIV medications
What is another name for a vaginal suppository?
Pessary
What is the purpose of a base for a vaginal suppository? What are the common bases used?
- Dissolve in vaginal fluid and release drug
- Polyethylene glycol or glycero-gelatin
What is the typical weight of a vaginal suppository?
3-5 g
What do vaginal tablets often contain?
Bioadhesive polymers which help tablet adhere to vaginal mucosa
What is the purpose of a polymeric matrix in a vaginal tablet?
Absorbs water from vaginal fluid and swells to release drug
What are the common drugs found in vaginal gels/ointments/creams?
- Spermicides
- Antimicrobials
- Hormones
