dds vaginal

anatomy of the vagina (9)

1. part of female repro sys

2. betw the bladder and rectum

3. elastic and canal like organ

4. acidic pH —> 4.5

5. predominantly lactobacilli —> prod lactic acid and hydrogen peroxide

6. has vaginal rugae (ridges inside vagina) —> inc sa & drug retention

7. highly vascularised —> bypass 1st pass meta

8. mucus prod in vagina —> have hydrophilic glycogen, lactic acid, bacteria, enzymes. Vol and consistency changes dur menstrual cycle

9. has lipid rich cell mem —> prefer lipophilic drug molecules

pathways of drug transport (3)

1. transcellular

2. paracellular

3. receptor mediated transport

factors affecting transcellular (4)

1. lipophilicity

2. molecular size

3. transport proteins

4. drug formulations

factors affecting paracellular transport (2)

1. hydrophilicity

2. molecular size

factors affecting receptor mediated transport (4)

1. binding affinity

2. receptor density

3. drug conc

4. mem fluidity

types of vaginal dosage forms (4)

1. pessary

2. tablet

3. cream

4. ring

phases of the menstrual cycle (2)

1. follicular phase

2. luteal phase

what is follicular phase

• day 1-14

• acidic pH due early phase (menses)

• more alkaline pH dur late phase (prepare for ovulation & fertilisation)

what is luteal phase

• day 15-28

• prepare endometrium for fertilisation

• inc progesterone

• epithelial conditions change frm early to late luteal phase

places cyclic change affects (3)

1. vaginal epithelium incl mucosa

2. vaginal fluids (uterine, cervical, vascular tissue fluids)

3. vaginal pH

changes in vaginal epithelium incl mucosa

follicular

• gradually thicken, menses » ovulation

• more elastic & well moisturized

• Intercellular channel narrows

• Glycogen rich cells

luteal

• Gradually thins (ovulation >> menses)

• Less elastic

• Intercellular channel wides

• Dec in glycogen content

how does it affect vaginal drug delivery (3)

1. paracellular transport

2. receptor mediated transport

3. glycogen levels

changes in vaginal fluids

• Follicular phase

  • Gradual inc in vol 

  • Thin & watery

  • Inc in enzymes

• Luteal phase

  • Gradual dec in vol

  • Thick & sticky

  • Dec in enzymes

how does it affect vaginal drug delivery (3)

1. mucus vol

2. mucus viscosity

3. enzymes

changes in vaginal pH

• Follicular phase

  • Acidic pH dur early phase (menses)

  • More alkaline pH during late phase (preparation for ovulation & fertilisation) 

• Luteal phase

  • Alkaline pH throughout → encourage fertilization

how does it affect vaginal drug delivery (3)

1. solubility & dissolution rate

2. stability

3. drug absorption

formulation factors (2)

1. physiochemical factors

2. dosage form factors

physiochemical factors (4)

1. molecular size

2. pKa (ionisation of drug molecule)

3. stability in vaginal fluid

4. solubility in vaginal fluid

dosage form factors (2)

1. drug release

2. hydrophilicity of vehicle

extra stuff for pessary and tablet (3)

1. water based pessaries dissolve quicker w more vaginal fluid

2. oil based pessaries dissolve quicker w higher body temp

3. vaginal tab req moisture to breakdown

advantages of vaginal drug delivery (6)

1. local & systemic effect

2. red systemic side effects

3. avoidance of 1st pass meta

4. convenient and ease of use

5. sustained release

6. rapid absorption

disadvantage of vaginal drug delivery (3)

1. variable absorption

2. limited drugs

3. patient discomfort & acceptance