Pharmaceutical Manufacturing Handbook: Production and

VAGINAL DRUG DELIVERY SYSTEMS 827
fl uctuations seen with daily oral administration; (4) rings are not associated with
adverse local effects, including cytological and normal fl ora changes; and (5) contraceptive
rings may be removed from the vagina during sexual intercourse and up
to 2 h, without compromising their pharmacological effect [110 – 112] . Although
vaginal rings have been essentially investigated and used for the delivery of sexual
hormones with contraceptive purposes or as hormone replacement therapy, these
drug delivery systems can be also useful for the administration of other drugs
such as bromocriptine mesylate, danazol, oxybutynin, antigens, and microbicides
[113 – 117] .
In the 1960s, fi rst reports that implants made of polysiloxane, containing sexual
steroids, could release their content at constant rates in saline solutions provided
early information that led to the development of the fi rst vaginal rings [118] . Vaginal
rings were initially developed in the 1970s as contraceptives. The fi rst system was
composed of a silicone rubber ring containing medroxyprogesterone acetate as the
active substance [119] . Nonetheless, the fi rst vaginal rings have just recently reached
the market, due to several unpredictable obstacles such as formulation diffi culties,
safety issues, and poor ovulation suppression [120, 121] . Table 3 presents some
vaginal rings currently available in the market.
Vaginal rings may present several designs, as seen in Figure 4 . The fi rst
vaginal rings were made of a homogeneous matrix containing the mixture of
poly(dimethylsiloxane) (matrix - forming polymer) and the active drug, usually
referred as a matrix design. Unfortunately, these rings showed an initial burst effect
due to rapid release of the drug contained in the system ’ s surface followed by persistent
linear decrease of the drug release rate. This later phenomenon is related to
the gradually thickening of a drug - depleted boundary between the inner drug -
loaded region and the release surface, which is created by continuous drug release
from the outer layers. Thus, their use in clinical practice was compromised, namely
TABLE 3 Selected Vaginal Rings Currently Available
Commercial Active
Clinical
Name Substance(s) Indications Availability
Nuvaring Etonogestrel Contraception United States,
and ethinyl
Europe,
estradiol
Brazil, Chile
Progering Progesterone Contraception
in lactating
women
Chile
Femring Estradiol Relief of vaginal United States,
acetate and urogenital
symptoms in
menopausal
women
Netherlands
Estring Estradiol Relief of vaginal United States,
and urogenital Canada,
symptoms in Europe,
menopausal
women
South Africa
Company
Organon
Laboratorios
Silesia
Warner Chilcott
Laboratories
Pfi zer