Pharmaceutical Manufacturing Handbook: Production and

384 CONTROLLED-RELEASE DOSAGE FORMS
the applied fi eld was increased from 5 to 11 Hz, the release of BSA from ethylenevinylacetate
copolymer (EVAc) matrices slowed in a linear fashion. The rate of
release could be modulated by altering the position, orientation, and magnetic
strength of the embedded materials as well as by changing the amplitude of frequency
of the magnetic fi eld. The micromovement within the polymer produced
microcracks in the matrix and thus made the infl ux of liquid, dissolution, and effl ux
of the drug. Done repeatedly, this would allow the pulsatile delivery of insulin.
Another mechanistic approach based on magnetic attraction is the slowing down
of oral drugs in the gastrointestinal system. This is possible by fi lling an additional
magnetic component into capsules or tablets. The speed of travel through the
stomach and intestines can then be slowed down at specifi c positions by an external
magnet, thus changing the timing and/or extent of drug absorption into stomach or
intestines. Slowing down the passage of magnetic liposomes with a magnet actually
increased the blood levels of drug. Babincova et al. [129] developed magnetoliposomes
for triggered release of drug. In their delivery systems, they entrapped
dextran – megnetite and model drug 6 - carboxyfl uorescein in the liposomes and used
laser to trigger the release of drug. The magnetite absorbs the laser light energy to
heat the lipid bilayer above the gel – liquid crystal - phase transsition temperature Tc ,
which is 41 ° C for dipalmitoyl - phosphatidylcholine. Liposomes made from this lipid
release their content as soon as the temperature reaches this level. They have also
suggested that the absorption of laser energy by magnetite particles provides a
means for localized heating and controlled release of liposome with a single laser
pulse. This may have potential applications for selective drug delivery, especially to
the eyes and skin. Even though the magnetic - modulated therapeutic approach
is promising, it still needs very careful attention for a number of physical and
magnetism - related properties. The magnetic force, which is defi ned by its fi eld
and fi eld gradient, needs to be large and carefully shaped to activate the delivery
system within the target area. The magnetic materials should be tissue stable
and compatible.
Chemically Induced Release
Gluose - Responsive Insulin Release Device A decrease in or the absence of insulin
secretion from pancreatic islets is the cause of diabetes mellitus. An effective glucose -
responsive insulin delivery system should be composed of a glucose - sensing component
and an insulin - releasing component. The sensing component detects a change
in the glucose level and produces a signal that affects the releasing component. The
magnitude of the signal increases with increasing glucose concentration, and so does
the rate of insulin release. Based on this principle, various polymer - based glucose -
responsive delivery systems have been designed, most of which are hydrogels that
can alter their volume and degree of hydration in response to glucose concentration.
Several systems have already been developed which are able to respond to glucose
concentration changes, such as glucose oxidase (GOD), which catalyzes glucose
oxidation [130] . Glucosylated insulin bound to concanavalin (Con) A was released
through exchange with external glucose, due to the difference in their binding constants.
This system needs direct injection of microcapsules into the peritoneal cavity
of patients, which may cause undesirable side effects arising from the immune
response to Con A if Con A was directly exposed to immune systems after breakage