Vaginal Drug delivery Flashcards
What are the layers found in the vagina?
- Epithelial layer- Non cornified stratified squamous cells composed of 5 layers
- Lamina Propria- dense connective tissue containing collagen fibres, fibroblasts, macrophages, mast cells and lymphocytes. It contains a blood supply and lymphatic drainage
- Mucosal layer
- Tunica Adventitia - consists of loose connective tissue
. Explain which physiological factors may affect the efficiency of vaginal drug delivery
- Menstrual changes in vaginal epithelium, as FSH and LH
- Pregnancy – increased thickening of epithelial layer, and has a lower pH
- pH of 4-5 is controlled by lactic acid produced via microflora. pH is highest during menstruation which affects ionisation and absorption of drugs
- Enzyme activity which is influenced by the ovarian cycle. Its activity is lower than that of the GI tract
- Transport route of the drug such as endocytosis, paracellular, transcellular
- Presence of vaginal fluid (cervical fluid and secretion from Bartholin gland)
- Post-menopausal women mitosis decreases so vaginal epithelium becomes thin, and cell boundaries are less distinct. The vagina is more likely to be invaded by leukocytes
- Thickness and tightness of epithelium is increased during proestrus and estrus. However, during metestrus and diestrus phase, epithelium is thinner which increases permeability
What physicochemical factors affect vaginal drug delivery?
- Hydrophilic compounds show high absorption via paracellular route (high absorption during mestris and diestrus)
- Macromolecules go via endocytosis
- Lipophilic compoiund move transcellularly
What are factors affected with the dosage form?
- Drug release
- Effective contact area
- Contact time (bioadhesiveness)
- Concentration
What are advantages of vaginal drug delivery?
- large surface area
- Rich blood supply
- Low metabolic activity
- Ease of administration
- Locally acting for local conditions
- Prolonged retention
- Permeation
What are disadvantages of vaginal drug delivery?
- Limited to highly potent biologicals
- Local irritation
- Hormone dependent changes
- Leakage of drug
- Life cycle constraints
Why is vaginal delivery of oestrogens and progesterones advantageous?
Progestational agents have poor oral bioavailability due to 1st pass effect
e.g.) Estradiol vaginal ring
Outline vaginal delivery of prostaglandins
PGE2 used to ripen cervix for labour induction
Cervidil vaginal insert is a controlled release pessary. It is made by a cross-linked polymer that swells in vaginal fluid and releases PGE2
Name two examples of drugs that can be delivered vaginally
Clotrimazole - antifungal cream
Metronidazole - anti-bacterial gel
Outline bioadhesives for vaginal drug delivery
- Mucoadhesive
- Prolongs contact time of drug with mucosal surface
- Increases local concentration
- Protects drug from dilution and degradation
Give an example of a bioadhesive used for vaginal drug delivery
Polycarbophil:
- Polyacrylic acid lightly cross-linked with divinyl glycol
- Uses inclue dry vagina, bacterial vaginosis
Name some advances in vaginal drug delivery
- STI protection
- Contraceptives
- Anti-infectives
- Systemic drug absorption
What are multi-segementated vaginal rings and its advantages?
- Each segment has different drug e.g.) progesterone, oestrogen
- Increases permeability, bioavailability
- Increases half life
- Allows large molecules to pass through such as GnRH
