International Journal of PharmTech Research

CODEN (USA): IJPRIF

ISSN : 0974-4304
Vol. 3, No.2, pp 1033-1044, April-June 2011

A Review on Novelty and Potentiality of

Vaginal Drug Delivery
Ananta Choudhury*, Sujoy Das, Mousumi Kar
Pharmaceutics Department, GRY Institute of Pharmacy, Vidya-Vihar,
Borawan, Khargone-451228

*Corres.author: [email protected]

Abstract: The objective of this review is to describe the potentiality of vaginal route and the current status of several
intravaginal delivery systems. A number of exhaustive efforts have been made toward the administration of drugs, via
alternative routes, that are poorly absorbed after the oral administration. The vagina as a route of drug delivery has been
known since ancient times. In recent years, the vaginal route has been rediscovered as a potential route for systemic
delivery of peptides and other therapeutically important macromolecules. A great deal of interest has been notice in the
design and application of different dosage forms via the vaginal route. Several studies have proven that the vagina is an
effective route for drug administration intended mainly for local action, but systemic effects of some drugs also can be
attained. The major advantages of this route include accessibility, good blood supply, the ability to bypass first-pass liver
metabolism, and permeability to large molecular weight drugs, such as peptides and proteins. This review, therefore,
summarizes various vaginal drug delivery systems with an introduction to vaginal physiology and factors affecting drug
absorption from the vaginal route.
Keywords :Vagina, Intravaginal delivery, HIV, Vaginal formulations.

Introduction
The present status of research and drug
development is mainly focused on invention of new
drug delivery systems and exploits different possible
routes of drug delivery which will provide a huge
degree of safety and optimum efficacy. Literature
shows that over a last few decade vagina remain to be
a relatively unexplored route of drug administration,
though as a site of drug delivery it offers certain
unique features that can be exploited in order to
achieved desirable therapeutic effect. Traditionally
from the past few decade vaginal routes is used mainly
for the local pharmacological effect, eg: antimicrobial,
spermicidal etc. Until 1920s vagina was considered to
be an organ incapable of absorbing drugs
systematically, 1, 2 but the mucous permeability and
dense network of blood vessels has made vagina an
excellent route of drug delivery for both local and

systemic effect 3, 4. Some of the typical delivery

systems administered via vaginal route include
solution (foam, douches), aerosols, semisolids,
(creams, ointments, gels), tampons, tablets, capsules,
peccaries,
suppositories,
particulate
systems,
intravaginal rings, sponges and powders5.
The research work till done on this route of
drug delivery system shows that, the permeation
mechanism for most of the active substances are
follows mainly diffusion. Whereas majority
hydrophobic substances are mainly absorbed through
intracellular route, while hydrophilic one are
preferably absorbed by pores present in the vaginal
mucosa6. In addition to that permeability of the vagina
is strongly influenced by the estrogen concentration,
which influence the pharmacokinetics of drug
designed for systemic action7.

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

1034

FIG-1 UTERUS AND UTERINE TUBE

The main advantages of vaginal drug delivery

are mainly, avoidance fast pass metabolism,
gastrointestinal irritation and side effect at
gastrointestinal tract. It is easy to administrated and
also provide a scope of self administration8. It has been
found that Low molecular weight drugs shows higher
permeability through this delivery system. However
drug delivery through this route having several draw
backs like low bioavailability, gender specificity,
culture sensitivity, personal hygiene, local irritation,
influence of sexual inter course and most importantly
changes of physiological condition depending upon
age need to be considered during the design of vaginal
formulation9.
The present scenario shows that despite of
several drawbacks, potentially important features of
drug delivery via vaginal route gaining a growing
interest in the field of research and development.
Currently most of the works of vaginal delivery
systems are mainly related to sexually transmitted
diseases and prevention of HIV infections.

Vaginal Anatomy, Histology and Physiology

The vagina is a female genital organ, plays an
important role in reproduction. Based on the literature
we can describe vagina as a slightly S-shape fibro
muscular, tubular organ, that approximately 6-10 cm
long and extended from the cervix of the uterus to the
vestibule10, 11. As per radiographic colpographic study

vagina is a slightly curved organ with two distinct

positions; a lower convex portion and a wider upper
portion that lies in an almost horizontal plane at
standing position of subject12, 13. The angle between
upper and lower axes is about 130 degree. When
vagina enters to the pelvis region it passes through two
diaphragms; the urogenital diaphragms and the
pubococcygeus from the pelvic diaphragms, act as
sphincters to the vaginal introitus. The women of
reproductive age having numerous folds in vagina,
named rugae, which provide distensibility, support
as well as increase surface area of vaginal wall14.
Vagina is mainly consisting of two type of nerve
supply. Among this one is peripheral, which primarily
supply to the lower quarter of the vagina and make it a
highly sensible area. An autonomic fiber is the other
one responds to stretch and are not very sensitive to
pain. Due to this only women rarely feel localized
sensation or any discomfort when they uses vaginal
products like suppositories, tampons, vaginal ring etc.,
and often unaware of the presence of such items in the
vagina1. The vascular supply of vagina constructed of
extended arteries that cover the vagina from multiple
sources. One of the major features of vascularity of
vaginal tissue that as attracted attention recently is the
postulation of a fast uterine pass effect, or direct
preferential vagina to uterus transport. A significantly
higher concentration of progesterone in uterus after
vaginal administration as compare to oral

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

administration can be taken as an evidence for the

above findings15.
The vaginal histology is mainly consisting of four
distinct layers. An estimated cell turnover of vagina is
about 10-15 layer in order of 7 days. The superficial
layer is mainly composed of nonsecretory stratified
squamous epithelium; its thickness varies with age and
several hormonal activities. The next is lamina propria
or tunica, made of collagen and elastin, which contains
a rich supply of vascular and lymphatic channels. The
muscular layer is third, with smooth muscle fibers
running in both circular and longitudinal directions.
The final layer consists of areolar connective tissue
and a large plexus of blood vessels16, 17. Vaginal tissue
does not contain fat cells, glands or hair follicles 18.
The vaginal physiology is mainly influence by
age, hormonal balance, pregnancy, pH changes and
concentration of microflora. Literature shows that
major changes will be take place in vaginal physiology
with age, like thickness of epithelium layer,
concentration of several enzymes, and production of
vaginal fluid and extent of vaginal discharge19. Human
vaginal fluid mostly transudes from vaginal and
cervical cells20, which mainly contain enzymes,
enzyme inhibitors, proteins, carbohydrates, amino
acids, alcohols, hydroxyl-ketones and aromatic
compounds21. The composition of fluids is effected by
cyclic changes caused by hormonal influence and state

1035

of arousal, which can alter the drug release pattern

from vaginal drug delivery system22. The thickness of
vaginal epithelium, amount and composition of vaginal
fluid also changes throughout the menstrual cycle. In
general Vagina maintains a pH between 3.8-4.8, which
influence by frequency of coitus, presence of cervical
mucus and the amount of vaginal transudate10. The
lactic acid produced from glycogen by lactobacillus
present in vagina plays an important role in maintains
acidic pH environment.

Factors Affecting Vaginal Absorption of Drugs

The drug transport across vaginal membrane
mainly takes place by three major ways, firstly
transcellularly via concentration dependent diffusion
through the cells, next is paracellularly mediated via
tight junctions and last one is vesicular or receptor
mediated transport. Drug absorption from vaginal
delivery system is mainly takes place in two main
steps: drug dissolution in vaginal lumen and membrane
penetration, so any factors related to physiology or
formulation that affects the above mentioned steps will
potentially alter absorption profile from vaginal drug
delivery. Some of the factors which influence the drug
absorption are discuss in the following portion.

FIG-2. Different Major Segmental Portion of Female Reproductive Organ.

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

Physiological Factors
Physiological factors like changes in the
thickness of epithelium layer, cyclic changes, changes
in the status of enzyme, hormones, volume of vaginal
fluid, alteration of vaginal pH and sexual arousal, as
describe earlier can potentially affect drug release from
any intravaginal delivery system and also alter its rate
of absorption. For e.g. vaginal absorption of steroids is
affected by the thickness of vaginal epithelium23.
Literature shows that vaginal absorption of estrogen
shows high in post menopausal women compare to
premenopausal women24. The high volume of vaginal
fluid may increase the absorption of poorly water
soluble drugs; however the same condition again
responsible to remove the drug from the vaginal cavity
and subsequent reduction of drug absorption. Further
cervical mucus, a glycoprotein gel can possibly be
exploited for bioadhesive drug delivery. However at
the same time it may serve as a permeability barrier for
different drug candidates25. Again changes in the pH of
vagina will alter degree of ionization of weak
electrolytic drugs and affect the release profile of pH
sensitive drugs26.

Physicochemical Factors
The physicochemical properties of drugs and
polymers like lipophilicity, ionization, molecular
weight, surface charge and chemical nature can
influence the vaginal drug absorption. Further the
affinity and bindings of drug with other related
component, introduced to prepare a dosages form is an
important factor, which can affect both the mass
transfer and bio-diffusion of drugs. A study by Owen
et al. shows that, diffusion of nonoxynol 9 into the
cervical mucus was increased by decreasing the pH,
whereas at low drug concentration mass diffusion
transfer tend to decrease with increasing osmolarity
and decrease with increase with increasing pH at the
same osmolarity27. In consideration to permeability
literature shows that lipophilic steroids like
progesterone and estrone having better permeability
than the hydrophilic one like hydrocortisone and
testosterone28. A study on vaginal absorption of
polyvinyl alcohol suggested a molecular weight range
above which compound will not absorbed and low
molecular weight lipophilic drugs are preferably more
as compare to high molecular weight lipophilic and
hydrophilic one, vaginal mucosal surface is very
specific in this respect. Experimental work till done on
vaginal permeability suggest that the drugs intended

1036

for vaginal deliver should have a certain degree of

aqueous solubility.

Different Drug Delivery System for Vagina

History shows that starting from the beginning
to till today selection of proper delivery system for
vagina to deliver the drug for specific disease
condition is an important factor in respect to rate and
extent of drug absorption and therapeutic efficacy.
Vaginal delivery is broadly categorized into two types:
drug delivery for local action and drug delivery for
systemic action. Delivery for local action are mainly
intended to treat local fungal infection, antimicrobial
therapy, spermicidal effect etc., and to achieved this
goal delivery systems like solutions, foams, gels,
creams are used. The present concept of vaginal
delivery is bit changed not only in respect to
improvement of conceptual local delivery of drugs but
also a revolutionary focus on systemic delivery of
drugs via vaginal route. Few years ago vaginal rings
were mainly used for systemic effect of drugs, but
today different novel concept like formulation based
on
polystyrene,
formulation
based
on
siliconelastomers, liposomal and submicron delivery
devices, prolong release vaginal rings, cubic and
environmental sensitive gel drug delivery systems, are
capable to provide systemic effect for a prolong period
of time. Hussain and Ahsan et al. concluded few
formulation systems intended for vaginal delivery for
different therapeutic agent are enlisted in table-1.
Jahnso and Masters show that the drug
distribution and coverage of vaginal tissue varies
considerably with the nature of delivery system29.
However quantitative measurement of drug after an
intravaginal administration is a difficult task and also
uncertain if administered formulation coated the whole
organ. Chatterton et al. perform an interesting study
introducing two radio labeled vaginal product, which
describe the retention and distribution of 99m TcDTPA labeled vaginal cream (reference product) and a
gel (experimental) dosages form, such study is use full
for understanding comparative distribution of different
formulated product29. This portion of the article is
mainly deals with the discussion different vaginal
delivery system used till date. Although different
vaginal product based on different delivery system are
still under development, there are few that have been
marketed for few years are summarized in the table -2.

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

1037

Table- 1. Some of the experimented vaginal drug delivery system9 .

Therapeutic
drug
Nonoxynol-9
Miconazole
nitrate

Intended use

Dosage form

Animal
model
Rabbit

Spermicide/topica
l contraceptive

Gel, Foam,
Cream

Anti-fungal

In-vitro

Comments
Detergent type spermicide,
irritation and increased risk of
infection

Prostaglandin
E2

Cervical ripening

Lactobacilli
strains

Urogenital tract
infections

Cream,
suppository,
swelling
controlled
release system
Crosslinked
PEG hydrogel,
suppository
Bi-layered
tablet

Progestin,
levonorgestrel
, orethindrone
acetate
Estradiol

Contraceptives

Vaginal ring

Human

Hormone
replacement
therapy
Cervical ripening

Vaginal ring

Human

Risk of endometrial
proliferation

Gel

Human

Decreased incidence of
cesarean deliveries, reduced
maternal-fetal morbidity
Chronic administrations
suppress secretion of ovarian
steroids

Relaxin

-----------In vitro

Onset of labor not always

predictable

In vitro

Restoration of normal vaginal

flora, good bacterial viability in
tablets
Uterine bleeding, hormonal
side effects, expulsions

LHRH

Hormone
dependent
mammary tumors,
fertility control

Suppository

Rat

Leuprolide

Ovulation
inducing activity

Rat

Insulin

Diabetes mellitus

Solution
suppository,
jelly
Solution, gel

Rat,
rabbit

Activity increased by 5 times

with addition of absorption
enhancers
Low bioavailability

Table 2. Commonly used marketed vaginal product 9.

Therapeutic Drug
(Brand Name)
Oxyquinoline
sulphate, ricinoleic
acid, acetic acid
(Acid Jelly )
Nonoxynol-9
(Advantages)
Etonogestrel,
ethinyl estradiol
(NuvaRing )

Intended Use

Dosage Form

Comments

Company

Maintenance of
vaginal acidity,
antiseptic

Vaginal gel

Maintain the pH 3.94.1.

Hope Pharmaceutical

Contraceptive

Vaginal gel

Contraceptive

Vaginal ring

Bioadhesive in
nature.
Commonly reported
adverse events are
vaginitis, weight
gain

Columbia
laboratories.
Organon

Nonoxynol -9
(Conceptrol)
Progesterone

Contraceptive

Vaginal gel

Infertility, secondary

Vaginal gel

Possible side effects

Advance Care
Product
Fleet Laboratories

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

(Prochieve)

amenorrhea

Clotrimazole
(Trivagizole)
Metronidazole
(Metrogel
Vaginal)
Progesterone
(Crinone)

Anti-fungal

1038

Cream

are breast pain,

constipation
Minor skin irritation

Taro Pharmaceuticals

Bacterial vaginosis

Vaginal gel

Vaginal discharge.

3M Pharmaceuticals

Infertility, secondary
amenorrhea

Vaginal gel

Serono

Estradiol
(Vagifem)
Dinoprostone
(Prostin E2)
Tioconazole
(Trivagizole)

Atropic vaginitis

Vaginal tablet

Bioadhesive
sustained release in
nature.
Mild allergic
reaction.

Labour inducer

Vaginal gel

Anti-fungal, vaginal
Candida infection

Vaginal ointment

Estradiol (Estring)

Hormone therapy

Vaginal ring

Dinoprostone
(Cervidil)

Induction of labor

Suppositories

Creams and Gels

A number research work has been done on creams and
gels as an intravaginal delivery system. They are
mainly used for topical delivery of contraceptives and
anti bacterial drugs. These delivery systems are messy
to use, uncomfortable, may not provide an exact dose
because of non-uniformity and leakage. Metronidazole
and clindamycin vaginal creams for the treatment of
bacterial vaginosis already proved them as efficacious
as oral delivery. Lamont et al. performed a randomized
controlled trial to evaluate the efficacy of clindamycin
cream and found this cream was well tolerated and
more efficacious than placebo.30 Marcus E Brewester
et al. reported a mucoadhesive cyclodextrin-based
cream formulation of itraconazole shows effective
therapeutic action on vaginal candidiasis31.
During past few years, considerable work has
been done on development of different gel drug
delivery systems which includes controlled release
hydrogel delivery, pH sensitive gel delivery, thermo
sensitive gel delivery systems etc. In hydrogel delivery
basically hydrophilic polymers forms network
structure by cross linkage via covalent bonding. A
swelling controlled intravaginal gel of miconazole has
been reported for anti fungal effect32. Again a 3%
alginate gel of nonoxynol-9 has been investigated for
intravaginal spermicidal activity and was found that
the spermicidal activity and diffusion of the active
agent changes with the pH and osmolarity of the
formulation33. Recently a gel microemultion based

Novo Nordisk
Pharmacia

Possible side effects

are swelling of face,
lips, tongue.
Can increase the
vaginal secretion
Side effect like
abdominal cramp,
diarrhea may occure.

Bristol Myers Squibb

Pharmacia and
Upjohn
Controlled
Therapeutics

formulation of spermicide with anti HIV effect of

zidovudine has been developed 34. literature shows that
minocaprin hydrogel formulations possess potent
microbicidal activity against HIV, HSV, Chlamydia
trachomatis and Neisseria gonorrhea, which is less
cytotoxic than nonoxynol-935,36. Cellulose acetate
phthalate (CAP) used the pharmaceutical industries as
enteric coating agent but recent study focused that its
having an potency to absorb and inactivate HIV-1,
HSV and other STIs 37. Further utilizing this ability of
CAP a potential anti-HIV vaginal gel formulation has
been formulated that are under phase II clinical trials
38
. An Intravaginal vaccine delivery by means of
vaginal gel is also reported, even intravaginal delivery
of cholera vaccine showed a greater mucosal response
in female genital tract compare to oral administration
of the vaccine 39. Further oxytoscin, dinoprostone and
misoprostol commonly used for cervical ripening and
induction of labor are also available in vaginal gel
form. A study by shetty et al. on the efficacy of
dinoprostone (prostaglandin E2) vaginal gel versus
vaginal tablet for the induction of labor shows
significant difference in the labor out comes between
two dosage forms 40. Several literatures show the
comparison of effectiveness between oral versus
vaginal administration of misoprostol. The dose
require for oral delivery of misoprostol is usually 4
times than that of intravaginal dose. However, there
have been few conflicting reports too with respect to
the efficacy of the route of misoprostol administration.
For example, Hall et al. reported that oral

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

administration misoprostol shows same potentiality to

induce labor and also safety and efficacy, as that of
vaginal administration 41, where as a study by shetty et
al. shows that vaginal administration of drug were
more efficacious than the oral route 42. Recently Chang
et al. conducted a study to determined the
thermosensitive behavior of clotrimazole vaginal gel
and found that thermosensitive gels are potential
candidate for safe, convenient and efficacious
treatment for vaginal candidiasis and also shows
mucoadhesive properties when prepared with mixture
of poloxamers and polycarbophil43. As per Edsman et
al. gels are one of the most commonly studied
mucoadhesive formulations for vaginal drug delivery.

Tablets and Suppositories

A large number of intravaginal delivery systems are
also available in the form of tablets and suppositories.
Some authors use the terms pessaries and suppositories
interchangeably and consider vaginal tablet as a
separate dosage form. These formulations are designed
to melt in vaginal cavity and release the active
constituent over prolong period of time. Suppository
systems are most commonly used to administer drugs
like dehydroepiandrosterone sulphate for ripening
effect on uterine cervix, miconazole for vaginal
candiasis and progesterone for hormonal replacement
therapy. Normal vaginal tablets contain similar
components as like conventional oral tablets, they are
easy to manufacture and insertion. Drugs that are
administered as vaginal tablets include itraconazole,
clotrimazole, metronidazole and prostaglandins.
Mucoadhesive polymers are sometimes used in vaginal
tablet formulation to increase the vaginal residence
time. Recently Mohd Afftab Alam et al. reported the
development of acid-buffering bioadhesive vaginal
tablet for the treatment of genitourinary tract infection
and was found that acid-buffering bioadhesive vaginal
tablet produce better antimicrobial effect than some of
the marketed intravaginal delivery system43. Literature
shows that polystyrene sulfonate (PSS) is also shows
superior antimicrobial activity against HIV and HSV,
therefore it is formulated in the form of vaginal tablet,
which will not immobilize sperm, not cytotoxic and
did not inhibit normal vaginal flora, so as proved as
potential delivery system44. Amal Ei-Kamel et al.
reported a chitosan and sodium alginate based
bioadhesive vaginal tablet of metronidazole45. Further
Gurpreet kaur et al. conducted a study on bioadhesive
vaginal clotrimazole tablet and concludes that
polymers like carbolpol-934P, sodium carboxymethyl
cellulose and sodium alginate are good candidate in
respect to bioadhesive vaginal tablet formulation46.
Literature shows that presence of hydrophobic and
release retarding materials may decrease the

1039

absorption of a drug from a vaginal formulation and

too hydrophobic drugs may not be suitable for vaginal
tablets. Further presence of penetration enhancers such
as surfactants, bile salts can significantly enhance
absorption.

Vaginal Ring
Vaginal rings are circular ring type drug delivery
devices designed to release drug in a controlled release
fashion after insertion in the vagina. This type of
device having several advantages like, it can be
controlled by the user, does not interfere with coitus
and allows continuous delivery of microbicidal
compounds. They are 5.5 cm in diameter with a
circular cross section diameter of 4-9 mm, where drugs
are homogeneously dispersed. Drugs at the surface of
the ring release faster than the drug in the inner layer.
The key challenge behind the development of this type
of device is finding the optimum dose that will deliver
the least amount of drug necessary to ensure
protection. To obtain constant release of drug from
vaginal ring sandwich or reservoir types of system
have been developed. Sandwich type devices consist
of a narrow drug containing layer located below the
surface of the ring and positioned between a nonmedicated central core and a non-medicated outer
band. In reservoir type of rings, drugs are dispersed in
a central core, which is than encapsulated by a drug
free layer. The materials introduced to fabricate
vaginal ring are mainly polymeric in nature. As per
literature most commonly used polymers for vaginal
ring are ploy (dimethylsiloxane) or silicon devices,
other elastomeric polymers such as ethylene vinyl
acetate and styrene butandiene block copolymer have
been tested in recent years47. Clinical acceptability of
ring made up of ethylene vinyl acetate is very high
because of its increase flexibility, improved optical
properties, greater adhesion and increased impact and
punch resistance49. Vaginal rings mainly used for
contraceptive and hormonal replacement therapy. For
most contraceptive application the ring is placed in
vagina for 21 days followed by a week of ring free
period. Nuvaring is one of the example of
contraceptive ring available in US market50. Further
Femring and Estring are the example of vaginal ring
intended for hormonal replacement therapy, release
estrogen. Literature reported that dapivurine, which is
also known as TMC120, is a potent non-nucleoside
reverse transcriptase inhibitor that is the only vaginal
ring system used as an intravaginal microbicide
delivery system for preventing the transmission of
STIs and HIV51.

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

Table no -3, Status of vaginal formulations in clinical trial stage 62.

Formulation
Phase
Purpose
Naphthalene 2-sulphonate
Phase I
Determine whether the vaginal gel PRO
(polymer) gel
2000/5 causes irritation when used
PRO 2000/5 gel
Phase I
Determine the safety and acceptability
when used by women;
Tenofovir PMPA gel
Phase I
Evaluate the PMPA gel in HIV-infected
and HIV-uninfected women
Effectiveness of BufferGel as Phases II
Compare BufferGel to Gynol II, a
a Vaginal
and III
currently available contraceptive ge
Contraceptive
1.0% C31G SAVVY
Phase III
Determine the effectiveness and safety
vaginal gel
for the prevention of male-to-female
transmission of HIV among women
6% cellulose sulphate
Phase III
Determine the effectiveness and safety
vaginal gel
for the prevention of HIV infection
Nonoxynol-9 (N-9) gel
Phase III
Determine if it can prevent the spread of
HIV

Bioadhesive Delivery System

Most of the conventional vaginal formulation
associated with several disadvantages of low retention
to the vaginal epithelium, leakage and messiness,
thereby causing poor patient compliance. To
circumvent these challenges bioadhesive vaginal drug
delivery system are being propagated. Bioadhesive
polymers that have been most commonly used for
intravaginal formulations include polycarbophil,
hydroxypropylcellulose and polyacrylic acid. The first
bioadhesive systems for vaginal drug delivery were in
the form of tablet for the delivery of bleomycin, an
anticancer agent. A bioadhesive polycarbophil gel,
Replens, is available in the market, which used to
retain moisture and lubricate vagina for 2-3 days and
maintain a healthy condition52. Attempt has also been
made to delivery of microbicides using bioadhesive
microparticulate vaginal system. Hyaluronic acid
based intravaginal delivery of calcitonin, a polypeptide
used in the treatment of postmenopausal osteoporosis,
have shown promise for intravaginal administration of
drugs for systemic effect53. A mucoadhesive controlled
release drug delivery system for nonoxynol-9, a
spermicidal agent, has been reported, which contain
various levels of nonoxynol-9 and EDTA, a chelating
agent, were formulated using carbopol 934P polymer
54,55
. A new mucoadhesive vaginal dosage form for the
antimycotic agent, clotrimazole, was developed by
incorporating
bioadhesive
polymers
like
polycarbophil, hydroxypropylemethylcellulose and
hyaluronic sodium salt into suppositories made up of
semi synthetic solid tri glycerides56.

1040

Status
Completed
In progress
In progress
In progress

In progress
In progress
In progress

Few Current Intravaginal Drug Delivery

Approaches
This part of the article is mainly focused on very
recent advancement and upcoming drug delivery
systems. SPL2008 (viva Gel TM) is a dendrimer-based
microbicide delivery system, in which dendrimer is
used not as a carrier but as an active ingredient 57 .
SPL7013 emerged as most promising dendrimer after
preclinical studies, which binds and blocks HIV-1
thereby preventing STIs, including HIV and genital
herpes, and has been formulated as a gel that is under
phase-I clinical trail 58. Development of monoclonal
human antibodies in the form of microbicidal gel for
protecting genital skin and epithelia against infection
by topical immunization is one of the major
achievement, this type of monoclonal synthetic
antibodies can be directly applied directly to the
genital skin and epithelia for protection from HIV and
other STIs pathogens 59 . PHI-444 a rationally designed
novel thiophen-thiourea basically a non nucleoside
reverse transcriptase inhibitor with potent activity
against HIV-1, formulated as intravaginal gel
formulation and found safe in rabbits. Further the
molecular condom is a recently developed anti-HIV
vaginal gel, which release anti-HIV bioactives upon
contract with the serum during sexual intercourse. It is
basically a hydrogel sensitive to body temperature and
pH, and serves as a smart semen-triggered vaginal
microbicide delivery vehicle, design to protect women
and unborn or nursing child from HIV60. A study has
been conducted on short interfering RNA (siRNA) as
potential liposomal microbicide delivery, where invitro test result shows that siRNAs are absorbed
throughout the vaginal tissue. This delivery system

Ananta Choudhury et al /Int.J. PharmTech Res.2011,3(2)

was design to target messenger RNA by

complementary base pairing and splits it in a selective
fashion, thus halting protein expression or viral
replication61. Some of the recently developed
microbicidal delivery systems, on which experiments
are carried out at clinical trial in different level, are
tabulated in table -3.

Conclusions
Although a number of research works has been done
on vaginal drug delivery system but till a huge task is
remain to be cover. Vagina as a route of drug delivery
is having several critical clinical obstacles, which
became a challenge to design appropriate drug delivery
system. In few aspect of macromolecular drug delivery
for vagina either locally or systemic shows significant
promise as well as acceptance within the female

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population. Among the several vaginal delivery

systems, vaginal gels, advance prolong action vaginal
rings and recently novel bioadhesive vaginal delivery
systems are already prove there potentiality. With the
increasing number of novel polymers, rationally
applied drug design in each year will definitely move
vaginal delivery system one step ahead in way of
success. Based on the research performances done till
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drug delivery going to play a vital role in order to
protect from the major pandemic disease of the world,
HIV. In this review we summarized the continues
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