Pharmaceutical Manufacturing Handbook: Production and

CLINICAL USAGE AND POTENTIAL OF VAGINAL DRUG DELIVERY 849
administration of these drugs [282] . For instance, Estring (Pharmacia & Upjohn), a
currently marketed vaginal ring containing low - dose estradiol (releases 7.5 μ g/day
when placed in the vagina), proved to be effi cacious, well tolerated, and safe when
used for up to a year in the treatment of urogenital symptoms in postmenopausal
women [283, 284] . This silicone polymer ring has a diameter of 55 mm and a cross -
sectional diameter of 9 mm and is used up to three months. Another similar ring
containing estradiol acetate (Femring, Warner Chilcott), with a diameter of 56 mm
and a cross - sectional diameter of 7.6 mm, is also currently available.
Estrogens and progestogens have also been administered through the vagina in
order to manage other conditions. In fact, vaginally administered progesterone is
commonly used for luteal - phase support in women undergoing assisted reproduction
treatment, allowing optimal uterine concentrations without the high serum
levels observed by other routes (oral and intramuscular), possibly due to the fi rst -
uterine - pass effect [285] . Several drug delivery systems such as capsules, tablets,
vaginal suppositories, or gels have been used and have been shown to be equally
effi cacious in increasing the chance of becoming pregnant. Nonetheless, sustained -
release formulations allow fewer administrations per day with lower doses [286] .
Also, progesterone vaginal rings have been successfully used for luteal - phase
support [287] .
5.12.6.4 Spermicides
The vaginal use of spermicidal substances during sexual intercourse is perhaps the
oldest method of contraception. However, the introduction of oral contraceptives
and the intrauterine device in the 1960s led to the decay in their use. Since many of
these substances also offer protection against sexually transmitted diseases, interest
and investigation in this fi eld have recently increased [288] . Also, the development
of new potential spermicides, namely antibodies [289] , contributed to further awareness.
Currently used spermicides include nonoxynol - 9, octoxynol, benzalkonium
chloride, and chlorhexidine.
Nonoxynol - 9 has been used for more than 30 years as a spermicide in over - the -
counter vaginal products, such as semisolid formulations, sponges, foams, fi lms, and
others, in order to prevent pregnancy. Although relatively safe and effective, nonoxynol
- 9 formulations are still not able to achieve the same decrease in pregnancy
risk obtained with hormonal methods [290] . Thus, some strategies have been used
to enhance nonoxynol - 9 effects while reducing its toxic effects. For instance, some
synergistic associations with chelating agents that have themselves little spermicide
activity, such as EDTA and ethylene glycol tetraacetic acid (EGTA), have been
shown to be promising in this matter [291] . Also, coprecipitation of nonoxynol - 9
with polyvinylpyrrolidone by a freeze - drying method can be useful, particularly
when the formulation of a solid system is desirable, as this process is necessary to
alter the chemical state (liquid to solid) of nonoxynol - 9 [292, 293] . Using these
coprecipitates, a tablet with an inner core that provides slow release of nonoxynol - 9
after its fast release of the outer core was shown to be an effi cient and safer way of
delivering this spermicide in rabbits [294] .
Semisolid formulations are often used as contraceptives, particularly gels. These
drug delivery systems were demonstrated to be useful, namely in reducing the toxicity
of nonoxynol - 9 [295] . Adequate formulation of these products has also been