Vaginal Drug Delivery Flashcards
Vagina anatomy
low pH - 4-5 therefore retards microbial growth
Vast network of blood vessels
Blood supply is direct to the systemic circulation
Drawbacks is that only 50% of population can use
Benefits of vagianal drug delivery
- Avoidance of fisrt pass circulation because Blood supply is direct to the systemic circulation
- Controlled release therefore longer dosing intervals
- Easy insertion and removal using application devices
- Only low doses are required due to no first-pass (10% of oral dose) thereofre less side effects
- Local effects to treat infection
- Less pain and damage than parenteral route
- les systemic side effects due to low doses.
How does the vaigina anatomy affect drug absorption?
-Vaginal rugae is uneven to incresae surface area for improved drug absorption.
-Epithelial barrier thickness - depends on age (thinner pre-puberty and post-menapausal)
-Pores in the barrier can appear mid-cycle
Mucus: affects pH - viscosity varies with age, increases pre-ovulation, decreases post-ovulation. Changes will significanlty affect the absorption of drugs.
-Enzymatic activity: less than in stomach, but will affect the degradation of drugs. activity varies with stages of cycle and age
-Arterial supply and venous drainage: vagina abundant with arteries, blood vessels, and lymphatic vessels - NO FIRST PASS METABOLISM
-Absotrption route: can be paracellular or trancellular. Hydrophilic favour paracellular.
what are the Formulation considerations:
physiochemical considerations
Drug release
Contact area and time
What are the physiochemical considerations?
- Solubility, dissolution rate, charge, molecular weight and aggregation are all important
- Low volume of mucus in vagina - will affect drug release
- permeability increased for lipophilic drugs and steroids (weak lipophilic)
What are the drug release considerations?
Rate limiting step is the drug release from formulation, espsecially with a tablet.
What is the contact area and time considerations?
Depends on size of dosage form and spreading
Bioadhesion will increase contact time - polymers that stick to the surface inside the vagina and prolonging drug contact time.
What are the type of drugs administered to the vagina?
Local or systemic =
- steroids
- Prostaglandins - labour induction and pregnancy termination
- Antimicrobials - metronidazole
- Proteins/peptides - insulin, TSH
What are the steroids administered via vagina?
Very useful as oral dosing is extensively metabolised (First-pass) so increased biavailibility this way.
Used for urogenital atrophy (thinning), contracecption, premenstrual syndrome, post-natal depression, HRT etc.
Oestrogens and Progesterones
Steroids are ususally formulated as creams and hydrogels and administered with an applicator.
Types of vaginal dosage forms:
1) Pessaries
2) Vaginal tablets
3) Vaginal capsules
4) Microspheres.
What do we know about pessaries?
formulated by moulding or direct compression
microbial contamination must be minimised
bases with gelatin must be heated to 100 degrees for 1 hour.
Glycerinated gelatin bases preferred as better tolerated - PEGs can be irritant
Administered with an aucillary application device (not used in suppositories)
What do we know about vaginal tablets?
Similar to uncoated tablets but larger and heavier
Major constituent is lactose (converted to lactic acid in situ which decreases pH)
Manufactured in the same way as oral tablets
Must disintegrate in situ so disintegrants are used because low mucus vol in the vagina.
What do we know about vaginal capsules?
They are soft gelatin capsules e.g. progesterone capsules
What do we know about microspheres?
These are within a gel. There is potential for protein/peptide delivery (e.g. calcitonin)
Polymers can be added to increase bioadhesion
CAn be used as a non-hormonal product for urogenital atrophy.
