J Pharm Educ Res Vol. 1, Issue No.

2, December 2010

Gastroretentive drug delivery technologies: Current approaches and future

potential
Amit Kumar Nayak1* Jadupati Malakar2 and Kalyan Kumar Sen3
1
Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj, Orissa, India
2
Department of Pharmaceutics, Bengal College of Pharmaceutical Science and Research, Durgapur, West Bengal, India
3
Department of Pharmaceutics, Gupta College of Technological Sciences, Asansol, West Bengal, India

Received September 28, 2010; Accepted November 11, 2010

ABSTRACT
The success of controlled oral drug deliveries is associated with some physiological adversities like short gastric
residence time and unpredictable gastric emptying time. Prolonged gastric residence increases duration of drug
release, reduces drug waste, and improves drug solubility in gastric pH. This has triggered attention towards
development of gastroretentive drug delivery technologies to deliver narrow absorption window drugs with
improved bioavailability. The present review addresses briefly about the current status of various leading
gastroretentive drug delivery technologies, developed until now, i.e. high density (sinking), floating, bio- or
mucoadhesive, expandable, unfoldable, super porous hydrogel, magnetic systems etc. In addition, important
factors controlling gastroretention, advantages and finally, future potential are discussed.

Key words: Gastroretention; Floating dosage forms; Controlled oral delivery; Drug delivery systems

INTRODUCTION after crossing the absorption window, the released drug

goes to waste with negligible or no absorption. This
Despite tremendous advancements in the drug
phenomenon drastically minimizes the time available for
delivery research, oral route remains the preferred route
drug absorption after it, which is then accompanied by
of administration of drugs because of low cost of therapy,
lesser bioavailability. Thus, the success of oral controlled
ease of administration, patient compliance etc. During the
drug delivery has faced some difficulties related with
past few decades, numerous oral delivery systems have
physiological adversities, like short gastric residence time
been developed to act as drug reservoirs from which the
(GRT) and unpredictable gastric emptying time (GET)1.
active substance can be released over a defined period
Prolonged GRT improves bioavailability, increases the
of time at a predetermined and controlled rate. It is evident
duration of drug release, reduces drug waste, and improves
from the recent scientific and patent literature that an
the drug solubility that are less soluble in a high pH
increased interest in novel oral controlled release dosage
environment2-3. This has triggered the attention towards
forms that designed to be retained in the upper
the development of various gastroretentive drug delivery
gastrointestinal tract (GIT) for a prolonged and predictable
technologies to deliver narrow absorption window drugs
period of time exists today in both academic and industrial
with improved bioavailability.
research groups.
Gastroretentive dosage forms are designed to be
A major constraint in oral controlled drug delivery is
retained in the gastric region for prolonged time and release
that not all drug candidates are absorbed uniformly
incorporated drug candidates and thereby enable
throughout the GIT. Some drugs are absorbed in a
sustained and prolonged input of the drug to the upper
particular segment of GIT only or are absorbed to a
part of the GIT thus ensuring its optimal bioavailability.
different extent in various segments of GIT. Such drug
Thus, they not only prolong the dosing intervals, but also
candidates are said to have an absorption window. But,
increase the patient compliance beyond the level of existing
in case of narrow absorption window drugs, only the
controlled release dosage forms. This application is
drug released in the region preceding and in close vicinity
especially effective in delivery of sparingly soluble and
to the absorption window is available for absorption. Again
insoluble drugs. Gastroretentive dosage forms greatly
*Email: amitkrnayak@yahoo.co.in
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J Pharm Educ Res Vol. 1, Issue No. 2, December 2010
improved the pharmacotherapy of the GIT through local
drug release, leading to high drug concentrations at the
gastric mucosa (eradicating Helicobacter pylori from
the submucosal tissue of the stomach), making it possible
to treat gastric and duodenal ulcers, oseophagitis etc
reducing the risk of gastric carcinoma and administer non-
systemic, controlled release antacid formulations4. Thus,
this technology has generated enormous attention over
the last few decades owing to its potential application to
improve oral delivery of some important drugs for which
prolonged gastroretention can greatly improve their oral
bioavailability5. Many technological attempts have been
made to devise various controlled release gastroretentive
drug delivery systems namely, high density (sinking)
systems that is retained in the bottom of the stomach6,
low density (floating) systems that causes buoyancy in
gastric fluid 7 , mucoadhesive systems that causes
bioadhesion to stomach mucosa8, unfoldable, extendible,
or swellable systems which limits emptying of the dosage
forms through the pyloric sphincter of stomach 9,
superporous hydrogel systems10, magnetic systems11 etc.
The review deals with the current approaches and future
potential of various gastroretentive technologies along with
anatomical and physiological aspects in their designing,
important factors controlling gastroretention, and
advantages.
ANATOMICAL AND PHYSIOLOGICAL
ASPECTS OF GASTRORETENTIVE DOSAGE
FORMS
A. Stomach: The site for gastroretention: The
stomach anatomy and physiology contain
parameters to be considered in the development of
gastroretentive dosage forms. The stomach is
located in the left upper part of the abdominal cavity
immediately under the diaphragm. Its size varies
according to the amount of distension: up to 1500
ml following meal; after food has emptied, a
collapsed state is obtained with resting volume of
25-50 ml. The stomach is anatomically divided into
three regions, fundus, body and antrum (pylorus).
The proximal part made of fundus and body serves
as a reservoir for undigested material, whereas the
distal part (antrum) is the key site for mixing motions
and acts as a pump for gastric emptying by propelling
action7.
2
B. Gastrointestinal utility and emptying of food:
The process of gastric emptying occurs both during
fasting and fed states, however the pattern of
motility differs markedly in the two states. During
fasting state an interdigestive series of electrical
events take place, which cycle both through the
stomach and intestine every 2 to 3 hours12. This is
recognized as interdigestive myeloelectric cycle or
migrating myeloelectric cycle (MMC), which is
further divided into four consecutive phases as
explained by Wilson and Washington13.
Phase I (Basal phase), the quiescent period, lasts
from 40 to 60 minutes and is characterized by a
lack of secretary, electrical and contractile activity.
Phase II (Preburst phase) lasts for 40 to 60 minutes
with intermittent action potential and contractions.
As the phase progresses, the intensity and
frequency also increases gradually.
Phase III (Burst phase) is a short period of intense
large regular contractions, termed as house keeper
waves that sweep off undigested food and lasts
for 4 to 6 minutes.
Phase IV is the transition period of 0-5 minutes
and occurs between phases III and I of 2
consecutive cycles.
After the ingestion of food, the pattern of contractions
changes from fasted to that of fed state. This is known
as digestive motility pattern and comprises continuous
concentrations as in phase II of fasted state. These
contractions result in reducing the size of food particles
(> 1 mm), which are propelled towards the pylorus in
suspension form. During the fed state onset of MMC is
delayed resulting in slowdown of gastric emptying rate14.
FACTORS CONTROLLING GASTRO-
RETENTION OF DOSAGE FORMS
The important parameters affecting the gastroretention
of oral dosage forms include: density, size and shape of
the dosage form, food intake and its nature, caloric content
and frequency of intake, posture, gender, age.
A. Density of dosage forms: GRT is a function of
dosage form buoyancy that is dependent on the
density of dosage forms. Dosage forms having a
density lower than the gastric contents can float in
J Pharm Educ Res Vol. 1, Issue No. 2, December 2010
the gastric fluids and hence experience
gastroretention, while high density systems sink to
bottom of the stomach. Both positions may isolate
the dosage system from the pylorus. A density of
< 1.0 gm/cm 3 is required to exhibit floating
property2.
B. Shape and size of the dosage form: Shape and
size of the dosage forms are important in designing
indigestible single unit solid dosage forms. In most
cases, the larger the dosage form the greater will
be the GRT due to the larger size of the dosage
form would not allow this to quickly pass through
the pyloric antrum into the intestine15. Dosage forms
having a diameter of more than 7.5 mm show a
better gastric residence time compared with one
having 9.9 mm4. Ring-shaped and tetrahedron-
shaped devices with a flexural modulus of 48 and
22.5 kilopounds/inch2 are reported to have a better
GRT (90% - 100% at 24 hours) as compared with
other shapes4.
C. Food intake and its nature: Food intake, viscosity
and volume of food, caloric value and frequency of
feeding have a profound effect on the
gastroretention of dosage forms. Usually the
presence of food in the GIT improves the GRT of
the dosage form and thus, the drug absorption
increases by allowing its stay at the absorption site
for a longer period. GRT can be increased by 4-10
hours with a meal that is high proteins and fats.
Again, increase in acidity and caloric value slows
down GET, which can improve the gastroretention
of dosage forms16. GRT can increase by over 400
minutes when successive meals are taken are given
compared with a single meal due to the lower
frequency of MMC.
D. Effect of gender, posture and age: Generally
females have slower gastric emptying rates than
male. The effect of posture does not have any
significant difference in the mean GRT for
individuals in upright, ambulatory and supine state.
In case of elderly persons (over 70 years), gastric
emptying is slowed down17.
Again, sleep, body mass index (BMI), physical activity
and diseased states of the individual (e.g. diabetes,
gastrointestinal diseases, Chrons disease) and
3
administration of drugs with impact on gastrointestinal
transit time for example drugs acting as anticholinergic
agents (e.g. atropine, propantheline), Opiates (e.g.
codeine) and prokinetic agents (e.g. metclopramide,
cisapride.) can alter gastroretension of oral dosage
forms18.
POTENTIAL DRUG CANDIDATES FOR
GASTRORETENTIVE DRUG DELIVERY
SYSTEMS
1. Drugs that have narrow absorption window in GIT
(e.g. L-DOPA, p-aminobenzoic acid, furosemide,
riboflavin) 2-3.
2. Drugs those are locally active in the stomach (e.g.
misroprostol, antacids) 3.
3. Drugs those are unstable in the intestinal or colonic
environment (e.g. captopril, ranitidine HCl,
metronidazole) 3,19.
4. Drugs that disturb normal colonic microbes (e.g.
antibiotics used for the eradication of Helicobacter
pylori, such as tetracycline, clarithromycin,
amoxicillin) 20-22.
5. Drugs that exhibit low solubility at high pH values
(e.g. diazepam, chlordiazepoxide, verapamil) 3,23.
DIFFERENT GASTRORETENTIVE
TECHNOLOGIES
Floating drug delivery systems (FDDS)
Drug delivery systems that float immediately upon
contact with gastric fluids present promising approaches
for increasing drug bioavailability with absorption windows
in the upper small intestine. FDDS have a bulk density
less then gastric fluids and so remain buoyant in the
stomach without affecting gastric emptying rate for a
prolonged period of time and the drug is released slowly
as a desired rate from the system. After release of drug,
the residual system is emptied from the stomach. This
results in an increased GRT and a better control of the
fluctuation in plasma drug concentration24. However,
besides a minimal gastric content needed to allow the
proper achievement of the buoyancy retention principle,
a minimal level of floating force (F) is also required to
keep the dosage form reliably buoyant on the surface of
the meal25. The major requirements for floating drug
J Pharm Educ Res Vol. 1, Issue No. 2, December 2010

delivery system are26: components and drug candidates within tablet matrix
(Figure 1)34. These have a bulk density lower than the
It should release contents slowly to serve as a
gastric content and therefore achieve buoyancy in the
reservoir.
stomach unflattering the gastric emptying rate for a
It must maintain specific gravity lower than gastric prolonged period of time. The drug is released from the
contents (1.004 1.01 gm/cm3). matrix tablet in a sustained manner at a desired rate. Even
It must form a cohesive gel barrier. after completion of the drug release, the residual system
is to be expelled from the stomach.
The inherent low density can be provided by the
entrapment of air (e.g. hollow chambers) 27 or by the
incorporation of low density materials (e.g. fatty materials
or oils, or foam powder) 28-29. The good floating behavior
of these systems could be successfully combined with
accurate control of the resulting drug release patterns.
The single-unit floating dosage forms are associated with
problems such as sticking together or being obstructed in
the GIT, which may produce gastric irritation. However,
multiple-unit floating systems may be an attractive Figure 1. Intra gastric single-layered floating tablet
alternative since they have been shown to reduce inter-
and intra- subject availabilities in drug absorption as well Intragastric bi-layered floating tablets: Intra
as to lower the possibility of dose dumping30. Based on gastric bi-layered floating tablets may be compressed
the mechanism of buoyancy, two distinctly different which contains the gas generating mechanism in one
technologies, i.e. non-effervescent and effervescent hydrocolloid containing sustained release layer and
systems have been utilized in the development of FDDS31. immediate release layer (Figure 2)35.

A. Effervescent systems: Effervescent systems

utilize gas (CO2) generating agents (e.g. sodium
bicarbonate, citric acid or tartaric acid) to achieve
floatability. After oral administration in the GIT, CO2
is liberated from these drug delivery systems, which
reduces the density of the system and making it
float on the gastric fluid 32 . The optimal
stoicheometric ratio of citric acid and sodium
Figure 2. Intra gastric bi-layered floating tablet
bicarbonate for gas generation is reported to be
0.76: 12,4,25. The buoyancy can be achieved also by Multiple-unit type of floating pills: A multiple-unit
utilizing matrices prepared with swellable polymers type of floating pill, which generates CO2 gas, has been
like methocel, hydroxypropyl methylcellulose developed (Figure 3)36.
(HPMC), chitosan 2,25 . An alternative is the
incorporation of the matrix containing portion of
liquid, which produce gas that evaporate at body
temperature33. These effervescent systems further
classified as gas generating systems and volatile
liquid/vacuum systems.
1) Gas generating systems:
Intragastric single-layered floating tablets: They
are formulated by intimately mixing the CO2 generating
Figure 3. Multiple-unit floating oral pill
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J Pharm Educ Res Vol. 1, Issue No. 2, December 2010
The system consists of sustained release pills as seeds
surrounded by double layers. The inner layer was an
effervescent layer containing tartaric acid and sodium
bicarbonate. The outer layer was a swellable membrane
layer. Moreover, the effervescent layer was divided into
two sub layers to avoid direct contact between these
two gas generating agents. Sodium bicarbonate was
contained in the inner sub layer, while tartaric acid was in
outer layer. When the system was immersed in buffer
system at 37C, it sank at once in the solution and form
swollen pills, like balloons (density < 1 gm/ml), which float
as they have lower density. This lower density is due to
generation and entrapment of CO2 within this system
(Figure 4).
Figure 4: Mechanism of floating behavior of multiple-unit floating
oral pill
2) Volatile liquid or vacuum containing systems:
Intra gastric osmotically controlled floating
delivery systems: The osmotic pressure controlled floating
systems consist of two compartments: a drug reservoir
compartment and an osmotically active compartment
(Figure 5).
Figure 5: Intra gastric osmotically controlled floating delivery systems
The drug reservoir compartment is enclosed by a
pressure responsive collapsible bag, which is impermeable
to vapor and liquid. This compartment also have an drug
delivery orifice. On the other hand, the osmotically active
compartment contains an osmotically active salts and is
enclosed within a semipermeable housing. In the stomach,
5
the water in the gastric fluid is continuously absorbed
through the semipermeable membrane into osmotically
active compartment to dissolve the osmotically component.
The osmotic pressure is then produced, which acts on
the collapsible bag and in turn forces the drug reservoir
compartment to reduce its volume and activate the release
of drug candidates in form of solution through the delivery
orifice. The floating support is also made to contain a
bioerodible plug that erodes after a predicted time period
to deflat the support. The drug delivery system is then
emptied from the stomach37-38.
Gas filled floating delivery systems: Gas filled floating
delivery systems include incorporation of a gas filled
floatation chamber, which may be vacuum or filled with
air or a harmless gas into a microporous component
that houses a drug reservoir (Figure 6)25. Apertures or
openings are present along the top and bottom walls
through which the gastric fluid enters to dissolve the drug,
while the other two walls in contact the fluid are sealed,
so that the undissolved drug remains therein.
Figure 6: Gas filled floating delivery systems
A. Non-effervescent systems: Non-effervescent
FDDS are normally prepared from gel-forming or
highly swellable cellulose type hydrocolloids,
polysaccharides or matrix forming polymers like
polyacrylate, polycarbonate, polystyrene,
polymethacrylate, carbopol, HPMC, sodium
alginate, chitosan etc. These systems can be further
divided into following sub-types:
1) Hydrodynamically balanced systems (HBS):
Sheth and Tossounian 39 first designated the
hydrodynamically balanced systems. HBSs have
gained a lot of importance in recent days to improve
absorption of drugs especially those are absorbed
from stomach and small intestine or drugs such as
weak bases, which dissolve better in the acid
environment of the stomach40. These systems
J Pharm Educ Res Vol. 1, Issue No. 2, December 2010
contain drug with gel-forming hydrocolloids meant
to remain buoyant on the stomach content. These
are single-unit dosage forms, containing one or more
gel-forming hydrophilic polymers. HPMC,
hydroxethyl cellulose (HEC), hydroxypropyl
cellulose (HPC), sodium carboxymethyl cellulose
(NaCMC), polycarbophil, polyacrylate, polystyrene,
agar, carrageenans or alginic acid are commonly
used excipients to develop these systems41. The
polymer is mixed with drugs and usually
administered in the HBS capsule. When the capsule
containing drug-hydrocolloid mixture comes in
contact with gastric fluid, the capsule shell dissolves
and the mixture swells to form a gelatinous barrier.
This imparts buoyancy in gastric juice for a long
period due to its continuous erosion of the surface,
which allows water penetration to the inner layers
maintaining surface hydration and buoyancy to the
dosage form (Figure 7) 41. Incorporation of fatty
excipients gives low-density formulations reducing
the erosion. Madopar LP, based on the system
was marketed during the 1980s42. Effective drug
deliveries depend on the balance of drug loading
and the effect of polymer on its release profile.
Several strategies have been tried and investigated
to improve efficiencies of the floating HBS.
Figure 7: Mechanism of hydrodynamically balanced systems as
FDDS
6
2) Microballoons (Hollow microspheres):
Microballoons (hollow microspheres) loaded with
drugs in their other polymer shelf were prepared
by simple solvent evaporation or solvent diffusion/
evaporation method to create a hollow inner core43
(Figure 8), which prolongs the GRT of the dosage
form. Commonly used polymers to develop these
systems are polycarbonate, cellulose acetate,
calcium alginate, Eudragit S, agar and low
methoxylated pectin etc. The polymer is dissolved
or dispersed in the organic solvent and the drug is
either dissolved or dispersed in the polymer solution.
The solution containing the drug is emulsified into
an aqueous phase containing polymers to form an
oil-in-water emulsion and after formation of stable
emulsion, the organic solvent is evaporated either
by increasing the temperature under pressure or
by continuous stirring. The solvent removal leads
to polymer precipitation at oil/water interface of
the droplets with formation of cavity, and thus,
hollow microspheres are formulated. Buoyancy and
drug release from dosage form are dependent on
quantity of polymers, the plasticizer polymer ratio
and the solvent used for formulation . The
microballoons floated continuously over the surface
of an acidic dissolution media containing surfactant
for >12 hours2. At present hollow microspheres
are considered to be one of the most promising
buoyant systems because they combine the
advantages of multiple-unit system and good
floating.
3) Alginate beads: Talukdar and Fassihi44 recently
developed a multiple-unit floating system based on
cross-linked beads. They were made by using Ca2+
and low methoxylated pectin (anionic
polysaccharide), or Ca2+ low methoxylated pectin
and sodium alginate. In this approach, generally
sodium alginate solution is dropped into aqueous
solution of calcium chloride and causes the
precipitation of calcium alginate. In an another
investigation, multiple-unit floating alginate beads
have been developed by from freeze-dried calcium
alginate using sodium alginate as the polymer and
calcium chloride as a cross-linking agent45. These
beads are separated and dried by air convection
and freeze drying, leading to the formulation of a
J Pharm Educ Res Vol. 1, Issue No. 2, December 2010
porous system, which can maintain a floating force
for over 12 hrs. These beads improve GRT more
than 5.5 hrs.
Figure 8: Formulation of floating hollow microsphere or
microballoon
High-density (sinking) system
Sedimentation has been employed as retention
mechanism for high-density systems that are small enough
to be retained in the folds of stomach body near the pyloric
region, which is part of the organ with lowest position in
an upright posture. This approach involves formulation
of dosage forms with the density that must exceed density
of normal stomach content (~ 1.004 gm/cm3). These
formulations are prepared by coating drug on a heavy
core or mixed with inert materials such as iron powder,
barium sulphate, zinc oxide and titanium oxide etc26. The
materials increase density by up to 1.5- 2.4 gm/cm3. A
density close to 2.5 gm/cm 3 seems necessary for
significant prolongation of gastric residence time46. But,
effectiveness of this system in human beings is limited.
Expandable, unfoldable and swellable Systems
Gastroretentivity of a pharmaceutical dosage form
can be enhanced by increasing its size above the diameter
of the pylorus (even in its widest state during a
housekeeper wave). If the dosage form can attain the
larger size than pylorus, the gastroretentivity of that dosage
form will be possible for long time. This large size should
be achieved fairly quickly; otherwise dosage form will be
emptied through the pylorus. Thus, configurations required
to develop an expandable system to prolong GRT are9,47:
i. a small configuration for oral intake,
ii. an expanded gastroretentive form, and
iii. a final small form enabling evacuation following
drug release from the device.
In addition they should be able enough to withstand
peristalsis and mechanical contractility of the stomach.
7
However, owing to significant individual variation, the cut-
off size cannot be determined exactly.
Unfoldable and swellable systems have been
investigated and recently tried to develop an effective
gastroretentive drug delivery. Unfoldable systems are
made of biodegradable polymers. The concept is to make
a carrier, such as a capsule, which extends in the stomach.
Caldwell et al, proposed different geometric forms like
tetrahedron48, ring49 or planar membrane (4-lobed, disc
or 4-limbed cross form) 49 of bioerodible polymer
compressed within a capsule. Klausner et al47,50, described
a gastroretentive delivery of levodopa, based on unfolding
polymer membranes that combines extended dimensions
(5 cm X 2.5 cm) with high rigidity. It is folded into large
gelatin capsule (00 or 000). The in vitro studies showed
that these delivery systems reached its unfolded form
within 15 minutes50. In humans, 67 % of the drug delivery
systems containing levodopa were retained in the stomach
during 5 hours50. These systems with extended size but
with lack of high rigidity are unable to retain in the
stomach, which may cause brief obstruction and
gastropathy. Therefore, rigidity of these systems is also
crucial parameter to design such a gastroretentive
delivery.
Swellable systems are also retained in the GIT due
to their mechanical properties. The swelling of dosage
form is usually resulted from osmotic absorption of water
and the dosage form is small enough to be swallowed by
the gastric fluid (Figure 9). In general, these size-increasing
drug delivery system potentially present the hazard of
permanent retention in the stomach and could lead to life-
threatening effects upon multiple administration. They are
also not cost-effective. A major advantage of these size-
increasing systems in the independence of their
performances on the filling state of the stomach.
Figure 9: Drug release from swellable systems
J Pharm Educ Res Vol. 1, Issue No. 2, December 2010

Bioadhesive or Mucoadhesive drug delivery
systems
Bioadhesive drug delivery systems are used to localize
a delivery device within the human to enhance the drug
absorption in a site-specific manner. In this approach,
various bioadhesive polymers are used and they can
adhere to the epithelial surface in the stomach51. Thus,
they increase GRT of the dosage forms. The basis of
microadhesion in that a dosage form can stick to the
mucosal surface by different mechanism. These
mechanisms52-53 are:-
i. The wetting theory, which is based on the ability of
bioadhesive polymers to spread and develop
intimate contact with the mucous layers.
ii. The diffusion theory, which proposes physical
entanglement of mucin strands the flexible polymer
chains, or an interpenetration of mucin strands into
the porous structure of the polymer substrate.
state during which, parameter evacuation of the dosage
form may occur42. Super porous hydrogels, average pore
size less than 100 m, swell to equilibrium size within a
minute, due to rapid water uptake by capillary wetting
through numerous interconnected open pores10.
Magnetic Systems
This approach to enhance the GRT is based on the
simple principle that the dosage form contains a small
internal magnet, and a magnet placed on the abdomen
over the position of the stomach. Although magnetic
system seems to work, the external magnet must be
positioned with a degree of precision that might
compromise patient compliance. Ito et al, used the
technological approaches in rabbits with bioadhesive
granules containing ultra-fine ferrite (-Fe2O3). They
guided them to oseophagus with an external magnet
(~1700G) for the initial 2 minutes and almost all the
granules were retained in the region after 2 hours54.

iii. The absorption theory, suggests that bioadhesion is Some gastroretentive products available in the market
due to secondary forces such as Vander Waal forces are listed in Table 1.
and hydrogen bonding. Table 1. Gastroretentive products available in the market.26, 55

iv. The electron theory, which proposes attractive Sl.No. Brand Name Active Ingredient(s)
electrostatic forces between the glycoprotein mucin 1. Cytotec
Misoprostal
net work and the bio adhesive material. 2. Cifran OD Ciprofloxacin

Gastric mucoadhesion does not tend to be strong 3. Oflin OD Ofloxacin

enough to impart to dosage forms the ability to resist the 4. Madopar L-DOPA and Benserazide
strong population forces of the stomach wall. The 5. Prolopa L-DOPA and Benserazide

continuous production of mucous by the gastric mucosa 6. Valrelease Diazepam
to replace that is lost through peristaltic contractions and 7. Conviron Ferrous sulfate

the dilution of the stomach content also seems to limit the 8. Topalkan Aluminum -magnesium antacid
potential of mucoadhesion as a gastroretentive force. The 9. Almagate FlatCoat
Aluminum -magnesium antacid
major challenge for bioadhesive drug delivery systems is 10. Liquid Gavison Aluminium hydroxide, magnesium
the high turnover rate of the gastric mucus in the GIT carbonate
and resulting limited retention times. Furthermore, it is
very difficult to target specifically the gastric mucus with ADVANTAGES OF GASTRORETENTIVE
bioadhesive polymers. Materials commonly used for DRUG DELIVERY SYSTEMS
bioadhesion are poly acrylic acid, polylactic acids, 1) Enhanced bioavailability: The bioavailability of
cholestyramine, HPMC, sodium CMC, chitosan, sodium therapeutic agents can be significantly enhanced
alginate, sucralfate, tragacanth, dextrin, gliadin, lectin etc. especially for those which get metabolized in the
upper GIT by gastroretentive drug delivery
Super porous hydrogel systems
approaches in comparison to the administration of
With pore size ranging, 10 nm to 10 m, absorption non-gastroretentive drug delivery. There are several
window by conventional hydrogel is a very slow process different factors related to absorption and transit
and several hours may be needed to reach an equilibrium of the drug in the GIT, that act concomitantly to
8
J Pharm Educ Res Vol. 1, Issue No. 2, December 2010
influence the magnitude of drug absorption2.
2) Sustained drug delivery: As mentioned earlier,
drug absorption from oral controlled release dosage
forms often limited by the short GRT available for
absorption. Gastroretentive dosage forms can
produce prolong and sustained release of drugs
from dosage forms. However, HBS or bioadhesive
or expandable systems type dosage forms can
remain in the stomach for several hours and
therefore, significantly prolong the GRT of
numerous drugs. For drugs with relatively short half
life, sustained release may result flip- flop
pharmacokinetics and also enable reduced
frequency of dosing with improved patient
compliance.
3) Site specific drug delivery: The controlled, slow
delivery of drug form gastroretentive dosage form
provides sufficient local action at the diseased site,
thus minimizing or eliminating systemic exposure
of drugs. This site-specific drug delivery reduces
undesirable effects of side effects. Hence they are
useful in the treatment of disorders related to
stomach and small intestine (e.g. eradication of
Helicobacter pylori).
4) Reduced fluctuation of drug concentrations:
Continuous input of the drug following controlled
release gastroretentive delivery produces systemic
drug concentrations within a narrower range
compared to the immediate release oral dosage
forms. Thus, fluctuations in drug effects are
minimized and concentration dependent side effects
that are associated with peak concentrations can
be prevented.
5) Improved selectivity in receptor activation:
The controlled release mode of drug administration
of gastroretentive systems have the important
feature that have an impact on the magnitude of
the pharmacologic response, which minimizes
fluctuation in blood drug concentrations (i.e.
between peak and trough). However, due to the
pronounced non-linear relationship between drug
concentration and pharmacologic effect (i.e.
pharmacodynamics) the impact of this property
differs considerably as a function of the shape of
the pharmacodynamic profile and the position of
9
the specific range of concentrations on the curve
of this profile. The minimizations of fluctuations in
drug concentrations also make it possible to achieve
certain selectivity in the elicited pharmacological
effects of drugs that can activate different receptors
at different concentrations.
FUTURE POTENTIAL
The control of drug release profiles has been a major
aim of pharmaceutical research and development in the
past two decades and might result in the availability of
new products with new therapeutic possibilities and
substantial benefits for patients. It is anticipated that
various novel products using gastroretentive drug delivery
technologies may enhance this possibility. Further
investigations may concentrate on the following concepts:
Design of an array of gastroretentive drug delivery
systems, each having narrow GRT for use according
to the clinical need, e.g., dosage and state of
diseases.
The quantitative efficiency of gastroretentive drug
delivery systems in the fasted and fed states.
Determination of minimal cut-off size above that
dosage forms retained in the GIT for for prolonged
period of time.
Design and development of gastroretentive drug
delivery systems as a beneficial strategy for the
treatment of gastric and duodenal cancers.
Development of various anti-reflux formulation
utilizing gastroretentive technologies.
Exploring the eradication of Helicobacter pylori
by using various antibiotics.
Design and development of gastroretentive drug
delivery systems for drugs, which are potential to
treat Parkinsons disease.
Study of the effect of various geometric shapes in
a more excessive manner than previous studies.
Design and synthesis of novel polymers according
to their clinical and pharmaceutical need.
Design and synthesis of novel mucoadhesive agents
to develop bioadhesive drug delivery systems for
improved gastroretention.
J Pharm Educ Res Vol. 1, Issue No. 2, December 2010
Design of novel mucoadhesive delivery using
various natural mucoadhesive agents according to
their clinical and pharmaceutical need.
CONCLUSION
Drug delivery using various gastroretentive
technological approaches have emerged as an efficient
means of enhancing the bioavailability and controlled
delivery of many drug candidates. The increasing
sophistication of these technologies will ensure the
development of numerous gastroretentive drug delivery
systems to optimize the delivery of drugs that exhibit
absorption window, low bioavailability and extensive first-
pass metabolism. Number of commercial product and
patents issued in this field are the evidence of it.
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