vaginal drug delivery system , mechanism , advantage , disadvantage and strategies of absorption improving

1. Vaginal Absorption

2. Introduction :
 The vagina, in addition to being a genital
organ with functions related to conception it
serves as a potential route for drug
administration. Mainly used for local action in
the vaginal region.
 It has the potential of delivering drugs for
systemic effects and uterine targeting

3. Anatomy of Vagina
 human vagina is often described as slightly
S-shaped fibromuscular tubes between 6-10
cm long and 2 cm wide extending from cervix
of the uterus to the vestibule
 The vaginal wall consists of three layers: the
epithelial layer, the muscular coat and the
tunica adventia
 Normal pH of the vagina in premenopausal
women ranges from 4 to 5, and rises to almost 7
in the post menopausal female.

5. Vaginal secretions
The vaginal secretion is a mixture of
several components such as
proteins/peptides, glycoproteins, lactic
acid, acetic acid, glycerol, glycogen
and ions such as Na++, Ca++ and Cl-

6. Types of vaginal dosage forms
vaginal semisolids: Creams
Gels
Ointments
Suppositories
vaginal liquids : Solutions
Suspensions
 vaginal aerosols
 vaginal controlled release formulations
Vaginal rings

7. Advantages of vaginal drug delivery
 Vaginal administration permits use of prolonged dosing,
with continuous release of medicaments
 Avoiding the fluctuations resulting from daily intake may
also lower the incidence of side effects.
 Alleviating the inconvenience caused by pain, tissue
damage and probable infection, it serves as a better
alternative to parenteral route.
 Vaginal route can be used for local as well as systemic
effect

8. Advantages of vaginal drug delivery
 avoidance of first pass effect
 avoidance of enzymatic deactivation in GIT
 large permeation area ,rich vascularization
and relatively low enzymatic activity.
 Non-invasive
 self-insertion and removal of the dosage
form like vaginal films, gel, pessaries, etc.

9. Disadvantages of vaginal drug delivery
 cultural sensitivity
 personal hygiene
 gender specificity
 local irritation
 influence of sexual intercourse
 Menstrual cycle-associated vaginal changes
 Sometimes leakage of drugs from vagina
and wetting of under garments

10. Absorption mechanism
 Drugs administered via the vaginal route are
absorbed
 Transcellularly via concentration dependent
diffusion through the cells.
 Paracellularly mediated by tight junctions.
 Vesicular or receptor mediated transport.
• Absorption of drugs from vaginal delivery
systems occurs in two main steps:
1. drug dissolution in vaginal lumen
2. membrane penetration.

11. Factors affecting the vaginal absorption
of drugs
1- Physiological factors
 cyclic changes affect in thickness of vaginal
epithelium
 fluid volume, viscosity and composition
 pH
 sexual arousal

12. Effect of pH changes on absorption
pH may change degree of ionization of drug and affect
their the absorption

13. Factors affecting the vaginal absorption
of drugs
2- Physicochemical properties of drugs
 Molecular weight
 lipophilicity
 ionization
 surface charge
 chemical nature
Ex : low molecular weight lipophilic drugs are likely to
be absorbed more than large molecular weight
lipophilic or hydrophilic drugs.

14. 3- Vaginal enzymes
 proteases are likely to be the prominent barrier for
the absorption of intact peptide and protein drugs
into the systemic circulation
 The human genital tract has lower enzymatic activity
leading to less degradation of protein and peptide
drugs in the vagina than the gastrointestinal tract
 sheep > guinea pig > rabbit ≥ human ≥ rat

15. Strategies to improve vaginal
absorption
A- Penetration Enhancers
Penetration enhancers are capable of
promoting absorption and penetration of drug
through the vaginal mucosa by decreasing
the penetration barrier
Currently, the most preferred penetration
enhancers include non-ionic surface active
agents, bile salts, benzalkonium chloride,
hyaluronic acid , polyethylene glycol.

16. Strategies to improve vaginal
absorption
B- Solubility Modifiers:
The poor solubility of drugs in vaginal fluid may affect
the release pattern of a drug from its device, which
influences the onset and therapeutic efficacy of the
drug.
Water-soluble drugs are good candidates for vaginal
drug delivery. The aqueous solubility of a drug can
be increased by several mechanisms such as
addition of solubilizing agents and cosolvency.
The most commonly used solubilizing agents include
citric acid, sorbitan, tween 80, polyoxyethylene
and sodium meta-phosphate.

17. Strategies to improve vaginal
absorption
C- Mucoadhesive agents:
- Mucoadhesive agents permit a close contact of
formulation with the vaginal mucosal surface by
promoting adherence .
- These include polycarbophil, hyaluronic acid,
chitosan, sodium alginate, tragacanth, carbomer,
acacia,
- Some of these polymers may possess site-specific
bioadhesive properties. For example, xanthan gum
and sodium alginate show site-specific bioadhesive
properties in a simulated vaginal environment

18. Strategies to improve vaginal
absorption
D- Nanotechnological Strategies
 nanosystems often potentiate the action of most active
constituents, reducing the required dosage and side
effects and improving the resulting activity
 which use nanoparticles ranging from1 to 100 nm in size.
Disadvantage
- expensive, and difficulties in some processes.
- depending on the size of the anonoparticles produced,
they may be easily inhaled, resulting in dangerous lung
diseases

19. nanotechnological processes
 liposomes (LIPs)
 microemulsions (MEs)
 hydrogel (HYD)
 polymeric nanoparticles(PNs)
 solid lipid nanoparticles (SLNs)

20. Viginal dosage forms:
 Vaginal creams , ointments and gels
 Vaginal Suppositories
 Vaginal liquids
 Vaginal Aerosols
 sustained/controlled-release drug delivery
 Vaginal Films
 Vaginal tablets

21. Vaginal semisolids:
 Vaginal creams , ointments and gels
 Topical vaginal preparations are used for mainly
conditions like infections, vaginitis, conditions of
endometrial atrophy & for contraceptive
purposes too.
 The vaginal topical preparations are mainly
applied by special applicators.
 Drugs like anti-infectives,hormones
contraceptives

22. Vaginal Suppositories
Solid suppositories are the most common dosage forms.
 the oval shape is more preferred.
 The most commonly used base for vaginal suppositories
consist of combination of the various molecular weight
polyethylene glycols & surfactants & preservatives are
added in them.
 They are buffered to acidic pH about 4.5.

23. Vaginal tablets
 Tablets are designed to rapidly disintegrate
in the vaginal cavity to release the active
drug.
 The normal vaginal tablets contain similar
components as like the conventional oral
tablets.
 Mucoadhesive polymers are sometimes used
in vaginal tablet formulations to overcome
the drawback of normal vaginal tablet

24. Vaginal liquids
The vaginal douches and solutions are also available in
market. They are used for cleansing of vagina.
 The unit dose douches are prepared which are
mixed with warm water and applied by inserters in
vagina.

25. Vaginal Aerosols
 Aerosols foams containing estrogenic substances &
contraceptive agents are available.
 The aerosol container has plunger which apply the foam
in the vaginal cavity.
 Marketed preparations like povidone-iodine vaginal
foam

26. Vaginal route for sustained/controlled-release drug
delivery
 are circular ring type drug delivery devices designed
to release drug in a controlled fashion after insertion
in the vagina.
 Contraceptive drugs

27. IN SITU GELLING
Mucoadhesive formulations prepared using
temperature-sensitive and mucoadhesive polymers,
poloxamer and polycarbophil.
 The water insoluble polymers
swells in vagina and form
bioadhesive gel on vaginal
layer.
 This allows continuous release
up to 25 to 50 hrs.

28. Vaginal Films
 Vaginal films are polymeric drug delivery systems shaped as thin
sheets, usually ranging from 220 to 240 μ m in thickness.
 These systems are often square (approximately 5 cm × 5 cm),
colorless, and soft, presenting a homogenous surface.
 Vaginal films are produced with polymers such as polyacrylates,
polyethylene glycol, polyvinyl alcohol, and cellulose
derivatives.

29. References:
1. The vagina as a route for systemic drug delivery
/Alamdar Hussain, Fakhrul Ahsan /Journal of Controlled
Release 103 (2005) 301–313
2. vaginal Mucosa – A Promising Site for Drug Therapy
/Vinita Vijay Kale1* and Alok Ubgade2 / British Journal of
pharmaceutical Research3(4): 983-1000, 2013
3. Vaginal drug delivery systems: /. DOBARIA1*, R.
MASHRU1 AND N. H. VADIA2 / East and Central African
Journal of Pharmaceutical Sciences Vol. 10 (2007) 3-13
4. The scope and potential of vaginal drug delivery/Kavita
Vermani and Sanjay Garg /3, No. 10 October 2000
5. Nanotechnological Strategies for Vaginal
Administration of Drugs / Journal of Biomedical
Nanotechnology · September 2015