Page 195 - Biomedical Engineering and Design Handbook Volume 2, Applications

174 MEDICAL DEVICE DESIGN

A
and the selectivity coefficient (K B ) is defined as
+
+
[ A ][ B ]
A
K = R + + + (6.21)
B
[ A ][ B ]
R
+
where [A ] = concentration of free counter ion
+
[B ] = concentration of drug bound of the resin
R
+
[B ] = concentration of drug freed from resin
+
[A ] = concentration of counter ion bound to the resin
R
Factors that affect the selectivity coefficient include type of functional groups, valence and nature of
exchanging ions, and nature of nonexchanging ions. Although it is known that ionic strength of GI fluid
is maintained at a relatively constant level, first-generation ion-exchange drug delivery systems had dif-
ficulty controlling the drug release rate because of lack of control of exchange ion concentration. The
second-generation ion-exchange drug delivery system (Pennkinetic system) made an improvement by
treating the drug-resin complex further with an impregnating agent such as polyethylene glycol 4000
to retard the swelling in water (Fig. 6.6b). These particles are then coated with a water-permeable poly-
mer such as ethyl cellulose to act as a rate-controlling barrier to regulate the drug release. 13
6.10 GASTRORETENTIVE DELIVERY SYSTEMS
Gastroretentive delivery systems were initially designed for oral delivery of antibiotics to the stomach
to combat Helicobacter pylori infections, which are found in the pyloric region of the stomach. But
later on, the delivery platform was utilized to deliver drugs with narrow window for absorption and
drugs intended for local action in the stomach like antacids. Drugs such as acyclovir, bisphosphonates,
captopril, furosemide, metformin, gabapentin, levodopa, baclofen, and ciprofloxacin have narrow
absorption window located in the upper intestine, and their absorption would be benefited from a
prolonged residence time of the drug at the site of absorption.
There are several approaches for gastroretention of dosage forms. Swelling and expandable dosage
forms, mucoadhesive beads, and floating beads are some of the strategies that have been used. Empting
of gastric content is controlled by contents in the stomach and size of the object being emptied. A fed
stomach empties slower than the fasted stomach. Thus, any dosage form administered with food will
be retained in the stomach for a longer period than administered in a fasted state. Objects larger than
20 mm in size tend to be retained in the fed stomach, which provides the basis for expandable and
swellable gastroretentive dosage forms. Swelling-type tablets are designed with polymers, which
undergo rapid relaxation in aqueous media, forming hydrogels from which the drug slowly diffuses out
into the gastric lumen. Expandable systems can be designed in different shapes, such as, films, strips,
propellers, and various other geometrical shapes, which form a part of the delivery system or are loaded
with drugs themselves. Upon contact with gastric fluids they expand by polymer relaxation to attain a
specific shape and render themselves resistant to gastric emptying. Another approach for the gastrore-
tention is mucoadhesion or bioadhesion to the gastric mucosa. Drug-loaded beads with mucoadhesive
coating stick to the gastric mucosa even after gastric emptying has taken place and continue to release
drugs from the matrix. Certain natural polymers, such as chitosan, possess amine groups that tend to
be ionized in the acidic gastric pH. The positively charged amine on chitosan interacts electrostatically
with the anionic mucus to provide bioadhesive property to the beads and microparticles of the delivery
system. Floating systems have also been explored for gastroretention. In these systems generation of
carbon dioxide gas in situ provides swelling and makes the system buoyant in the stomach. But two
major disadvantages encountered with the system make it a less-preferred alternative for gastroreten-
tion. Firstly, the floating system can only operate in a fed stomach where there is enough fluid held for
a considerable amount of time. A fasted stomach has little fluid and drinking water in a fasted state does
not simulate a fed state as the gastric contents are emptied almost immediately. Thus, the floating systems
cannot operate in the fasted state. Secondly, the patient has to be erect, either standing or sitting, after