GRDDS (Teksed)
GRDDS (Teksed)
GRDDS (Teksed)
Gastroretentive techniques
Several techniques, including
floating
swelling,
Bio/mocoadhesion
Floating systems
Floating systems, first described by Davis in 1968,
are lowdensity systems that have sufficient
buoyancy to float over the gastric contents and
remain in the stomach for a prolonged period
(23,24).
While the system floats over the gastric contents,
the drug is released slowly at the desired rate (25,
26), which results in increased GRT and reduces
fluctuation in plasma drug concentration (27).
Floating systems can be classified as effervescent
and noneffervescent systems.
Effervescent systems
Flotation of a drug delivery system in the stomach
can be achieved by incorporating a floating
chamber filled with vacuum, air, or an inert gas.
Gas can be introduced into the floating chamber
by the volatilization of at) organic solvent (e.g.,
ether or cyclopentane) or by the CO, produced as a
result of an effervescent reaction between organic
acids and carbonatebicarbonate salts
Noneffervescent systems
Noneffervescent systems incorporate a high level
(2075% w/w) of one or more gelforming, highly
swellable,:
cellulosic hydrocolloids (e.g., hydroxyethyl
cellulose, hydroxypropyl cellulose, HPMC, and
sodium carboxymethylcellulose),
polysaccharides,or
matrixforming polymers (e.g., polycarbophil,
Polyacrylates, and polystyrcne) into tablets or
capsules.
Bio/mucoadhesive systems
Bio/mucoadhesive systems bind to the gastric
epithelial cell surface, or mucin, and extend the GRT
by increasing the intimacy and duration of contact
between the dosage form and the biological
membrane.
The concept is based on the selfprotecting
mechanism of the GIT. Mucus secreted continuously
by the specialized goblet cells located throughout the
GIT plays a cytoprotective role.
Mucus is a viscoclastic, gellike, stringy slime
comprised mainly of glycoproteins. The thickness of
the mucus layer decreases from the membrane
surface to the GI lumen.
a.
b.
c.
1.
2. Bondingmediated-adhesion.
The adhesion of polymers to a mucus or epithelial
cell surface involves various bonding mechanisms,
including
physicalmechanical
bonding
and
chemical bonding.
a) Physicalmechanical bonds can result from the
insertion of the adhesive material into the crevices or
folds of the mucosa.
b) Chemical bonds may be either covalent (primary) or
ionic (secondary) in nature. Secondary chemical
bonds consist of dispersive interactions (i.e., van der
Waals interactions) and stronger specific interactions
such as hydrogen bonds. The hydrophilic functional
groups responsible for forming hydrogen bonds are
the hydroxyl and carboxylic groups (2).
Receptormediated-adhesion.
Certain polymers can bind to specific receptor sites
on the surface of cells, thereby enhancing the gas
tric retention of dosage forms. Certain plant lectins
such as tomato lectins interact specifically with
the sugar groups present in mucus or on the
glycocalyx.
Swelling systems
After being swallowed, these dosage forms swell
to a size that prevents their passage through the
pylorus . As a result, the dosage form is retained in
the stomach for a long period of time.
These systems are sometimes referred to as plug
type systems because they tend to remain lodged
at the pyloric sphincter. These polymeric matrices
remain in the gastric cavity for several hours even
in the fed state.
Highdensity systems
These systems, which have a density of 3
g/cm3, are retained in the rugae of the
stomach and are capable of withstanding its
peristaltic movements .
Above a threshold density of 2.42.8 g/cm3,
such systems can be retained in the lower
part of the stomach .
Evaluation of GRDDS
1. Floating systems
2. Bio/mucoadhesion systems
3. Swelling systems
Floating systems
1. Floating/buoyancy time.
The test for buoyancy is usually determined
in 900 mL of simulated gastric (HCI/NaCl
with 0.02% Tween 80, pH 1.2) or intestinal
fluids (KH2PO4/NaOH buffer with 0.02%
Tween 80, pH 7.4) maintained at 37 oC
using the USP dissolution apparatus. These
fluids simulate the surface tension of
human gastric juice (3550 mN/M2) .
2. Specific gravity.
The specific gravity of floating systems can be
determined by the displacement method, using
benzene as a displacing medium .
3. Resultant weight.
Until now, bulk density and floating duration
have been the main parameters to describe the
adequacy of a dosage form's buoyancy,
However, although the density value may
indicate whether or not an object will float, the
density value does not reflect the magnitude of
floating force produced by the object
F = Fbuoy Fgrav
F = dfgV dsgV (df ds) gV
F = (d f M/V) gV
in which F is the total vertical force
(resultant weight of the object), g is the
acceleration due to gravity, df is the fluid
density, ~ is the object density, M is the
object mass, and V is the volume of the
object.
Bio/mucoadhesion systems
Bioachesive strength.
The bioadhesive strength of a polymer can be
determined by measuring the force required to
separate the polymer specimen sandwiched
between the layers of either an artificial (e.g.,
cellophane) or biological (e.g., rabbit stomach
tissue) membrane .This force can be measured by
using a modified precision balance or an auto
mated texture analyzer.
Swelling systems
Weight gain and water uptake (WU). The
swelling behavior of a dosage unit can be
measured by studying its weight gain or
WU. The study is done by immersing the
dosage form in simulated gastric fluid at 37
oC and determining these factors at regular
intervals. The dimensional changes can be
measured in terms of the increase in tablet
diameter and/or thickness over time.