Pharmaceutical Manufacturing Handbook: Production and

818 VAGINAL DRUG DELIVERY
Menopausal women experience a decline in estrogens, which leads to several
changes in the genital organs, namely in the vagina. Such changes include atrophy
of the labia majora and shortening and loss of elasticity of the vaginal barrel. The
number of epithelial cell layers decreases (from 8 – 10 in premenopausal to 3 – 4 in
postmenopausal), leading to alterations in the barrier capacity and potential increase
of mucosal damage and pain and burning sensation during sexual intercourse.
Vaginal fl uids decrease approximately 50% because of the Bartholin glands atrophy
and a decrease in the number and maturity of vaginal cells. A decrease in the colonization
by lactobacilli species is observed in menopausal women as a result of the
reduction of vaginal glycogen levels, leading to a low production of lactic acid and
consequently to increased vaginal pH. In postmenopausal women without estrogen
treatment the vaginal pH is estimated to be 5.5 – 6.8 or even higher [37, 38] .
5.12.3
GENERAL FEATURES OF VAGINAL DRUG DELIVERY
Vaginal drug delivery is mostly used in gender - specifi c conditions, although it can
be a viable alternative for drugs usually administered by other routes. Also, traditionally
problematic drugs from a delivery point of view (e.g., peptides) may fi nd in
the vaginal route an interesting and promising way for nonparental administration.
Limitations and potentialities of vaginal drug administration are intimately connected
to this route ’ s idiosyncrasy. Hence, acquaintance of particular features of
vaginal drug delivery is required.
5.12.3.1 Advantages and Disadvantages of Vaginal Drug Delivery
The administration of drugs through the vagina, and eventually their absorption, is
a function for which this organ is not physiologically conceived. Nonetheless, the
vaginal route of administration presents some advantages. Substances absorbed
through the vaginal mucosa bypass the liver before entering systemic circulation,
avoiding hepatic fi rst - pass metabolism. Thus, drugs that undergo extensive hepatic
fi rst - pass metabolism can benefi t from vaginal administration, usually requiring less
amount of drug to achieve the same biological effects. Steroids used in hormone
replacement therapy or contraception are a good example of molecules that are
largely metabolized in the liver, with approximately 95% of orally administered
estrogens undergoing hepatic metabolism. Also, these molecules are able to damage
the liver when administered by the oral route, an event that can be minimized with
vaginal administration. Gastrointestinal side effects are common for many oral
administered drugs; the vaginal route may be an alternative to their administration,
with the benefi t of increased patient compliance. Additionally, vaginal enzymatic
activity is lower when compared with gastrointestinal activity, lacking even some
important enzymes enrolled in drug metabolism, such as trypsin and chymotrypsin.
The vaginal route offers women the possibility of easy self - insertion and removal
of drug delivery systems as well as avoidance of the pain, tissue damage, and eventual
infection often associated with parenteral routes. Ocular and buccal administration
sites frequently become irritated after prolonged contact with drug delivery
systems; conversely, the vagina presents less sensitivity, allowing the presence of
drug formulations for long periods of time. Although absorption of substances is