Pharmaceutical Manufacturing Handbook: Production and

RELEASE OF DRUGS FROM CONTROLLED-RELEASE DOSAGE FORMS 371
pilocarpine. The unit is placed in the eye and resides in the lowe cul - de - sac, just
below the cornea. Since the device itself remains in the eye, the drug is released into
the tear fi lm. The advantage of such a device is that it can control intraocular pressure
for up to a week. Controlled release is achieved with less drug and fewer side
effects, since the release of drug is zero order. However, it is diffi cult to keep it in
the eye for a longer time and can cause discomfort.
The prodrug administration is also getting attention as ocular controlled - release
dosage forms. Since the corneal surface presents an effective lipoidal barrier, especially
to hydrophilic compounds, it seems reasonable that a prodrug that is more
lipophilic than the parent drug will be more successful in penetrating this barrier.
Recently, dipivalyl epinephrine (Dividephrine), a dipivalyl ester of epinephrine, has
been formulated [78] . Epinephrine itself is poorly absorbed owing to its polar characteristics
and is highly metabolized. The prodrug form is 10 times as effective at
crossing the cornea and produces substantially higher aqueous humor levels.
New sustained technologies are also gaining much interest in ocular delivery, as
in other routes. Liposomes as drug carriers have achieved enhanced ocular delivery
of certain drugs, antibiotics, and peptides. Prolonged delivery of pilocarpine can be
achieved with a polymeric dispersion or submicrometer emulsions [79] .
5.1.9 VAGINAL AND UTERINE CONTROLLED - RELEASE
DOSAGE FORMS
Controlled - release devices for vaginal and uterine areas are most often for the
delivery of contraceptive steroid hormones. The advantages are prolonged release,
minimal side effects, and increased bioavailability. First - pass metabolism that inactivates
many steroid hormones can also be avoided.
Therapeutic levels of the medroxyprogestrone vaginal ring have been achieved
at a total dose that is one - sixth the required oral dose [80] . The sustained release of
progesterone from various polymers given vaginally has also been found useful in
cervical ripening and the induction of labor. A possible new use of the vaginal route
is for long - term delivery of antibodies. When various antibodies, including monoclonal
IgG, were administered from polymer vaginal rings in test animals, antibody
concentrations remained high over a month in vaginal secretions and detectable in
blood serum [81] .
The hormone - releasing devices in uterus have a closer resemblance to controlled
release because they involve the release of a steroid compound by diffusion [82, 83] .
Progesterone, the active ingredient, is dispersed in the inner reservoir, surrounded
by ethlene/vinyl acetate copolymer membrane. The release of progesterone from
this system is maintained almost constant for about a year [84 – 86] .
5.1.10 RELEASE OF DRUGS FROM CONTROLLED - RELEASE
DOSAGE FORMS
There are three primary mechanisms by which active agents can be released
from a delivery system: diffusion, degradation, and swelling followed by diffusion.
Any or all of these mechanisms may occur in a given release system. Probable