Vaginal

vaginal drug delivery

utilizes the vaginal cavity for drug absorption and effect at the site of application (local) or for systemic effect 

Describe the anatomical and physiological challenges posed by the vaginal routes of admin

• IUD requires doctor visit

• Route used to treat hormones or to treat infections 

• Target region: vaginal cavity 

Anatomic/ Physiologic Factor	Important considerations
Length and width	8-10 cm and 2 cm
Volume of fluids	2-3 mL
Vascularization	High
Surface area	Increases by presence of rugae and microridges
Thickness of epithelium	Varies cyclically in response to changes in hormones; effects drug dissolution and permeability
pH	Menstruating women: 3.5-4.5 (buffering capacity higher than non-menstrating women) Non-menustrating women: 6-7
Enzymatic activity	Low
Drug transport	Passive transcellular transport of UI molecules  Unionized: goes systemic Ionized: stays local

 Analyze the physicochemical characteristics needed for vaginal drug delivery 

MW	Log Ko/w	pKa
< 1000 Da	1-3	Determines the number of UI species Weak acid pH < pKa → mostly unionized pH > pKA → mostly ionized  Weak base  pH < pKa → mostly ionized pH > pKa → mostly unionized Women in reproductive years vs. non-reproductive

Analyze the formulation characteristics needed for vaginal drug delivery

• Formulations

  • Suppositories

    • Local action/ systemic effect 

  • Tablets

    • Local action/systemic effect

    • Dissolve slowly

    • Don’t leak

  • Rings

    • True extended release dosage form

    • Generally hormone therapy 

  • Ointments and creams 

    • Local action

    • Messy to use 

• Characteristics 

  • Volume of administration is low or about 1 suppositor

  • Leakage issues are common 

• Solubility and Dissolution Rate

  • Dissolution rate depends on the time of the month for menstruating women 

  • Need to dissolve slowly and diffuse down the concentration gradient 

  • Fats dissolution more likely to lead to leakage 

• Excipient

  • Mucoadhesives to increase viscosity and contact time 

  • Surfactants and co-solvants to maintain necessary solubility for duration of activity 

  • pH

    • Menstruating women - acidic

    • Non-menustrating women - neutral 

  • PEG bases: can be irritating for suppositories 

 Select the best formulation for a patient based on your understanding of vaginal drug delivery and patient specific factors 

• Patient needs med with long contact time → patient should take Rings 

• Tablets have more compliance that suppositories because they dissolve slower and suppositories have leakage issues

• For traveling- tablets are better because suppositories could melt 

• Local minor infections: creams, ointment, liquid

Adv/dis

local action

aimed at treating vaginal infections with antibiotic or antifungal or for relief of menopausal symptoms

systemic action

limited to relief of menopausal symptoms through the admin of hormones