3.3 - Vaginal DD

vaginal route local effect

used for vaginal infections, lubrication, contraception

vaginal route systemic effect

- not common route

- research ongoing

- good for highly metabolized drugs (no hepatic first pass effect)

vaginal dosage forms

liquids, semisolids, solids

liquid dosage form

douche

semisolid dosage form

creams, gels, ointments, foams

solid dosage forms

suppositories/compressed tablets (Pessary, Ovule, Insert), and film 

film dosage form

- rapidly disintegrating polymer sheet

- drug uniformly dispersed and dissolved

gross anatomy of vagina

- fibromuscular tube (6-10 cm long in adult)

- extends from cervix

vaginal mucosa

- stratified squamous epithelium (skin-like)

- contains rugae (folds → increase SA/aid in retention)

- contains natural microflora (Lactobacilli)

vaginal epithelium

- SC has dead corneocytes

- intercellular lipids present

- does NOT form impermeable intercellular lipid envelope

- more permeable than skin SC

mucous layer of vagina

- limited amount, complex fluid

- source = cervical secretions

- contains transudates, exfoliated cells, leukocytes 

pH of vagina

- generally low/acidic (due to lactic acid from Lactobacilli; bacteriostatic)

other features of the vagina

- presence of enzymes

- relatively limited SA (vs GI tract)

- venous drainage NOT to hepatic portal system (NO first pass)

Variations in Mucosa

- fluid amount/consistency varies (Menstrual cycles)

- pH is higher: age 4 wks to puberty or upon menopause

- epithelium thickness changes (thinner upon menopause)

systemic drug absroption

- good for some drugs (large molecules/peptides)

- limited for most current products

- significant interpatient variability 

- affected by mucosal variations

dosage form considerations

product pH, microbial presence, attributes post-administration, administration aids

product pH

- consider natural vaginal pH (acidic)

- formulate low pH to match if possible

- important for drug solubility and stability

- avoid strong buffer capacity (allows fluids to control pH)

Microbial Prescence

- must be free of microorganisms, yeast, and molds

- do NOT disrupt natural microflora

Attributes post-administration

- retention → long enough for distribution

- liquefaction → solids must melt/dissolve rapidly

- distribution → should spread well

- spreading ranking: foams/liquids > suppositories > disintegrating tablets

- leakage → should NOT be excessive or too quick

administration aids

- applicators usually required

- supplied w/ drug product

- products often designed for high insertion

Imvexxy

- estradiol vaginal inserts

- used for moderate to severe dyspareunia

Clotrimazole Vaginal Cram and Vagistat Ointment

used in treatment of Candidasis

Cleocin Suppository and Metronidazole Vaginal Gel

used in treatment of bacterial vaginosis

Crinone gel

- used as a progesterone supplementation

- bioadhesive gel (polycarbophil)

VCF Film

- fast-dissolving polymer film (nonoxynol-9)

- used in contraception