Home' Australian Pharmacist : Australian Pharmacist February 2011 Contents Vol. 30 -- February #02
core lengths depending on the
required release rate. The full or
partial core(s) is then encapsulated
with silicone elastomer in two stages
to produce the full reservoir ring.
Changing the length and diameter
of the core and the thickness of the
drug-free outer layer can modify the
rate at which the drug is released.35
Release of the drug is achieved by
the dissolution of the drug from
the core into the drug-free outer
layer then the diffusion of the drug
through the outer layer into the
surrounding medium. The release
rate is dependent on the solubility
(Cp) and the diffusion coefficent (Dp)
of the drug in the outer layer, which
can be represented by Equation 2.
After the recent success of the
Centre for AIDS Programme
of Research in South Africa's
(CAPRISA) clinical trial of the
Tenofovir gel, the current goal
of the HIV microbicide field is to
develop an antiretroviral-releasing
vaginal ring which should allow for
improved adherence among women.
Dapivirine has been successfully
released in vitro for 28 days36 and
71 days37 from a vaginal ring. A
phase I trial demonstrated that a
dapivirine vaginal ring formulation
was safe and well tolerated and that
release of the drug in vivo, at levels
several orders of magnitude above
its EC50 value, could be achieved.38
A phase II clinical trial of a 25 mg
dapivirine-loaded silicone vaginal ring
has finished recruiting volunteers
and should begin early in 2011.
However, the development of a
Tenofovir-loaded vaginal ring has not
been as straight forward. The highly
hydrophilic character of Tenofovir
(log P value of -2.5; water solubility
13.4 mg/mL) is not conducive to
release at therapeutically relevant
rates from conventional vaginal
ring polymers. In a bid to overcome
this obstacle, hydrophilic, water-
swellable polyurethanes, biosoluble
acacia gum and non-biodegradable
hydrogels are being evaluated
for the manufacture of Tenofovir-
releasing vaginal rings.39--40 Once an
antiretroviral releasing ring has been
developed and tested successfully
in human clinical trials, the next step
is to develop a ring that releases
multiple HIV microbicides in order
to reduce the chance of any HIV
resistant strains developing.
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future directions in medication delivery
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