Pharmaceutical Manufacturing Handbook: Production and

854 VAGINAL DRUG DELIVERY
made. Ideally, formulations should be easy and comfortable to use, colorless, odorless,
and messiness free. Also, products that are better retained in the vagina seem
to be favored by women, since leakage is one of the most undesired feature of
vaginal formulations [349] . Concerning preferred vaginal dosage forms, gels and
creams seem to be the most popular among women. On the other hand, vaginal
suppositories and tablets are among the most disliked dosage forms. Others, such
as fi lms, present ambiguous results, mostly related with diffi culties during insertion
[350, 351] . Vaginal rings have been shown to be highly acceptable by both women
and their sexual partners, even during sexual intercourse. A trial conducted in North
America and Europe showed that couples rarely felt the device during penile penetration,
and when the ring was noticed, almost none of the partners seemed to
mind [352] . Furthermore, insertion and removal of vaginal rings are judged to be
easy by users [353] .
Packaging and applicators may also infl uence women ’ s choice. Products that are
placed in the vagina by means of an applicator seem to be preferred because it
facilitates administration and avoids direct touching of genitalia during insertion.
Applicator characteristics, namely length, width, color, fi lling features (single - use or
reusable applicators), and ease of usage, are also known to infl uence women ’ s
acceptability [351, 354] .
5.12.8
VETERINARY VAGINAL DRUG DELIVERY
As with humans, veterinary vaginal drug administration has been performed for a
long time, particularly for the treatment of local infections, traditionally involving
the use of vaginal suppositories, liquid formulations, or gels. Advantages of this route
include the avoidance of damage to the skin or to tissue that is associated with
injections, minor stress infl icted to the animals, and possibility of ceasing drug delivery
at will [355] . Nonetheless, the fi rst major studies on veterinary drug delivery
have been performed by Robinson in the 1960s with progestogen - impregnated
polyurethane sponges [356] . Since then, the major use of the vaginal route has been
the control of the estrus cycle in livestock by delivering progestogens and estrogens
in a controlled fashion. Also, the administration of these hormones showed good
results in treating reproductive disorders, such as ovarian quiescence, cystic ovary
or cystic corpus luteum [357] . Estrus synchronicity is advantageous as it allows
insemination of all or selected females in a herd or fl ock to occur during a single
period of several hours or days [358] . With this purpose, several drug delivery
systems have been developed, being generally based on polymeric matrices that
are able to control release of drug content. These devices also present two common
features: Retention is guaranteed by means of a gentle pressure applied to the
mucosa and the existence of a mechanism (e.g., an attached string) that allows their
easy removal at the end of the treatment. Table 7 presents a synopsis of these
systems, as reviewed by Rathbone et al. [358, 359] . Also, some of these devices are
shown in Figure 9 . In addition to the vaginal administration of progestogens and
estrogens, delivery of other therapeutic agents through this route for both local and
systemic effects has been investigated, namely 1,25 - dihydroxy vitamin D3 [360] ,
lactic acid – producing lactobacilli [361] , antimicrobials [362] , local anesthetics [363] ,
and vaccines [364] .