Drug Delivery

ISSN: 1071-7544 (Print) 1521-0464 (Online) Journal homepage: http://www.tandfonline.com/loi/idrd20

Gastroretentive dosage forms: A review with

special emphasis on floating drug delivery systems

Vivek K. Pawar, Shaswat Kansal, Garima Garg, Rajendra Awasthi, Deepak

Singodia & Giriraj T. Kulkarni

To cite this article: Vivek K. Pawar, Shaswat Kansal, Garima Garg, Rajendra Awasthi,
Deepak Singodia & Giriraj T. Kulkarni (2011) Gastroretentive dosage forms: A review with
special emphasis on floating drug delivery systems, Drug Delivery, 18:2, 97-110, DOI:
10.3109/10717544.2010.520354

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Drug Delivery, 2011; 18(2): 97–110

REVIEW ARTICLE

Gastroretentive dosage forms: A review with special

emphasis on floating drug delivery systems
Vivek K. Pawar1, Shaswat Kansal1, Garima Garg1, Rajendra Awasthi1, Deepak Singodia2, and
Giriraj T. Kulkarni1
1
Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH- 58, Uttar Pradesh,
250002, India, and 2Manipal College of Pharmaceutical Sciences, Manipal, Karnatka, 576104, India

Abstract
In the present era, gastroretentive dosage forms (GRDF) receive great attention because they can improve
the performance of controlled release systems. An optimum GRDF system can be defined as a system which
retains in the stomach for a sufficient time interval against all the physiological barriers, releases active moi-
ety in a controlled manner, and finally is easily metabolized in the body. Physiological barriers like gastric
motility and gastric retention time (GRT) act as obstacles in developing an efficient GRDF. Gastroretention
can be achieved by developing different systems like high density systems, floating drug delivery systems
(FDDS), mucoadhesive systems, expandable systems, superporous systems, and magnetic systems. All these
systems have their own merits and demerits. This review focused on the various aspects useful in develop-
ment of GRDF including the current trends and advancements.
Keywords:  Gastroretentive drug delivery systems; floating drug delivery systems; mucoadhesive systems;
expandable systems; superporous systems; magnetic systems; dual working systems

Introduction important therapeutic options. GRDF are designed on

The oral route is the predominant and most preferable
route for drug delivery, but drug absorption is unsat-
isfactory and highly variable in the individuals despite
excellent in vitro release patterns (Davis, 2005; Streubel
et al., 2006). The major problem is in the physiological
variability such as gastrointestinal transit as well as GRT;
the later plays a dominating role in overall transit of the
dosage forms. GRT of the oral controlled release system is
always less than 12 h (Chawla et al., 2003). These aspects
lead to development of a drug delivery system which will
remain in the stomach for a prolonged and predictable
time.
Recent scientific and patent literature has shown
increased interest in novel dosage forms that can be
retained in the stomach for a prolonged and predicta-
ble period of time. One of the most feasible approaches
for this in the gastrointestinal tract (GIT) is to control
GRT using GRDF that will provide us with new and
the basis of one of the several approaches like formu-
lating low density dosage form that remain buoyant
above the gastric fluid (FDDS) or high density dosage
form that is retained at the bottom of the stomach,
imparting bio-adhesion to the stomach mucosa, reduc-
ing motility of the GIT by concomitant administration
of drugs or pharmaceutical exicipients, expanding the
dosage form by swelling or unfolding to a large size
which limits the emptying of the dosage form through
the polymeric sphincter, utilizing ion–exchange resin
which adheres to mucosa, or using a modified shape
system.
Drug targeting to the stomach can also be attractive
for several other reasons:
• To produce a prolonged local action on to the gas-
trodudonal wall for e.g. drugs used in the eradication
of H. pylori infection like amoxicillin (Bardronnet
et al., 2006).

Address for Correspondence:  Vivek Kumar Pawar, Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH- 58,
Uttar Pradesh, 250002, India. Tel: +91-9756354246. E-mail: vivekpharmaperson@gmail.com

(Received 17 May 2010; revised 21 July 2010; accepted 30 August 2010)

ISSN 1071-7544 print/ISSN 1521-0464 online © 2011 Informa Healthcare USA, Inc.
DOI: 10.3109/10717544.2010.520354 http://www.informahealthcare.com/drd
98   V. K. Pawar et al.
• For weakly basic drugs with poor solubility in a basic
environment.
• For drugs which have poor stability in the colon.
• For drugs which have a narrow absorption window.
• For the drugs which have primarily absorption in the
stomach.
 From the formulation and technological point of view,
FDDS is a considerably easy and logical approach in the
development of GRDF. Hence, this review article focuses
on the current technological development in FDDS with
special emphasis on its potential for oral controlled drug
delivery.
Gastrointestinal tract physiology
Stomach
The stomach is situated in the left upper part of the abdom-
inal cavity immediately under the diaphragm. Its size var-
ies according to the amount of distension: up to 1500 ml
following a meal; after food has emptied, a collapsed state
is obtained with resting volume of 25–50 ml (Waugh &
Grant, 2001). The stomach is anatomically divided into
three parts: fundus, body, and antrum (or pylorus). The
proximal stomach, made up of fundus and body regions,
serves as a reservoir for the ingested materials, while the
distal region (antrum) is the major site of mixing motions,
acting as a pump to accomplish gastric emptying.
Gastrointestinal motility
Two distinct patterns of gastrointestinal motility and
secretion exist corresponding to the fasted and fed states.
As a result the bioavailability of orally administered drugs
will vary depending on the state of feeding. In the fasted
state, it is characterized by an inter-digestive series of
electrical event and cycle, both through the stomach
and small intestine every 2–3 h. This activity is called the
interdigestive myoelectric cycle or Migrating motor com-
plex (MMC). MMC is often divided into four consecutive
phases: basal (Phase I), pre-burst (Phase II), burst (Phase
III), and Phase IV intervals.
• Phase I (basal phase) lasts from 40–60 min with rare
contractions.
• Phase II (pre-burst phase) lasts for 40–60 min with
intermittent action potential and contractions. As the
phase progresses the intensity and frequency also
increases gradually.
• Phase III (burst phase) lasts for 4–6 min. It includes
intense and regular contractions for short periods.
Due to this contraction all the undigested material is
swept out of the stomach down to the small intestine.
This is also known as the housekeeper wave.
• Phase IV lasts for 0–5 min and occurs between phases
III and I for two consecutive cycles.
 The motor activity in the fed state is induced 5–10 min
after the ingestion of a meal and persists as long as
food remains in the stomach. The larger the amount
of food ingested, the longer the period of fed activ-
ity, with usual time spans of 2–6 h, and more typically
3–4 h, with phasic contractions similar to Phase II
of MMC.
Emptying of dosage form from the stomach
To achieve gastric retention, the dosage form must resist
premature gastric emptying. For this, the dosage form
must be able to withstand in the stomach against the
force caused by peristaltic waves. Furthermore, once
its purpose has been served the dosage form should be
removed from the body with ease. Table 1 explains the
GIT transit time of various dosage forms.
Factors affecting gastric retention (Soppimath et al.,
2001b; Arora et al., 2005; Julan et al., 2005)
• Density: GRT is a function of dosage form buoyancy
that is dependent on the density.
• Size: Dosage form units with a diameter of more than
7.5 mm are reported to have an increased GRT com-
pared to those with a diameter of 9.9 mm.
• Shape of dosage form: Tetrahedron and ring shaped
unfolding expandable GRDF with a flexural modu-
lus of 48 and 22.5 kilo pounds per square inch
(KSI), respectively, are reported to have better GRT
≈ 90–100% retention at 24 h compared with other
shapes like continuous stick, planar disc, planar
multilobe, and string.
• Single or multiple unit formulation: Multiple unit
formulations show a more predictable release pro-
file and insignificant impairing of the performance
due to the failure of units, allow co-administration
of units with different release profiles or containing
incompatible substances, and permit a larger margin
of safety against dosage form failure compared with
single unit dosage forms.
• Fed state: Under fasting conditions, the gastrointesti-
nal motility is characterized by the periods of strong
motor activity or the MMC that occur every 2–3 h. The
MMC sweeps undigested material from the stomach
and, if the timing of administration of formulation
coincides with that of the MMC, then GRT of the unit
may be expected to be very short. However, in the

fed state, MMC is delayed and GRT is considerably
longer.
• Nature of meal: Feeding of indigestible polymers or
fatty acid salts like cellulose, starch, polydextrose,
and reffinose can change the motility pattern of
the stomach by delaying the MMC, thus decreas-
ing the gastric emptying rate and prolonging drug
release.
• Caloric content: GRT can be increased by 4–10 h with
a meal that is high in proteins and fats.
• Frequency of feed: The GRT can increase by over
400 min when successive meals are given com-
pared with a single meal due to the low frequency
of MMC.
• Gender: It was observed that mean GRT in males
(3.4 ± 0.6 h) is less than the female subjects (4.6 ± 1.2 h)
of same age and race. Females emptied their stomach
slowly in comparison to male candidates, regardless
of their weight, height, and body surface area.
• Age: Elderly people, especially those over 70, have a
significantly longer GRT.
• Posture: GRT can vary between supine and upright
ambulatory states of the patient. For the floating
systems it was reported that when subjects were
kept in the upright ambulatory position the dos-
age form stayed continuously on gastric content
in comparison to the supine state of the patients.
Thus, in the upright position of the patients float-
ing dosage forms protected against post-prandial
emptying.
• Concomitant drug administration: Clonidine, lith-
ium, nicotine, progesterone, anti-cholinergics like
atropine and propantheline, and opiates like codeine
prolong GRT. On the other hand, erythromycin and
octreotide enhance the gastric emptying.
GRDF
Dosage forms that can be retained in the stomach are
called GRDF. Over the last two decades, numerous GRDF
have been designed to prolong gastric residence time
(Talukder & Fassihi, 2004a). Figure 1 describes how the
drug absorption takes place in the case of conventional
dosage forms and GRDF.
Table 1.  Transit times of various dosage forms across the GIT.
Transit time (h)
Dosage form Stomach Small intestine
Tablets 2.7 ± 1.5 3.1 ± 0.4
Pellets 1.2 ± 1.3 3.4 ± 1.0
Capsules 0.8 ± 1.2 3.2 ± 0.8
Solution 0.3 ± 0.07 4.1 ± 0.5
Gastroretentive dosage forms   99
Classification of GRDF
They may be broadly classified into:
1) High density systems;
2) Floating systems;
3) Expandable systems;
4) Superporous hydrogels;
5) Mucoadhesive or bioadhesive systems;
6) Magnetic systems; and
7) Dual working systems.
High density 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 2.4–2.8 g/cm3, such systems can be retained in
the lower part of the stomach (Rouge et al., 1998). Results
of a clinical study showed that an enteric-coated sinking
ursodeoxycholic acid (UDCA) tablet formulation gives
better bioavailability in comparison to enteric-coated
floating tablets and hard gelatin capsule formulations of
UDCA in 12 healthy subjects. The area under the curve
[AUC, μmol/1 (8 h)] following oral administration of
enteric-coated, sinking UDCA (39.0 ± 8.5) was signifi-
cantly higher than that obtained after both conventional
UDCA (30.5 ± 4.9) and floating enteric-coated UDCA
(29.3 ± 3.4) (Simoni et al., 1995). These systems comprise
some drawbacks like, firstly, they are technically difficult
to manufacture with a large amount of drug because the
dry material of which it is made up of progressively reacts
or interacts within the gastric fluid to release its drug con-
tents and, secondly, till now, no such system is available
on the market (Garg & Sharma, 2003).
Swelling and expandable systems
The expandable GRDF are usually based on three con-
figurations: a small (‘collapsed’) configuration which
enables convenient oral intake; an expanded form that
is achieved in the stomach and thus prevents passage
Total through the pyloric sphincter; and finally another small
5.8 form that is achieved in the stomach when retention is
4.6 no longer required, i.e. after the GRDF has released its
4.0 active ingredient, thereby enabling evacuation (Groning
4.4 et al., 2007).
100   V. K. Pawar et al.
A B
GRDF
Mucoadhesive
system
Absorption Window
Due to gastrointestinal
motility negligible
absorption occur
Figure 1.  Drug absorption in the case of conventional dosage forms (A) and principles of GRDF (B).
The expansion can be achieved by swelling or by
unfolding in the stomach (Klausner et al., 2002). Swelling
usually occurs because of osmosis. Unfolding takes place
due to mechanical shape memory, i.e. the GRDF is fabri-
cated in a large size and is folded into a pharmaceutical
carrier, e.g. a gelatin capsule, for convenient intake. In the
stomach, the carrier is dissolved and the GRDF unfolds or
opens out to achieve extended configuration. The storage
should maintain unfoldable properties for extended time
spans (Kagan et al., 2006).
In spite of their interesting characteristics, expand-
able systems have drawbacks. Storage of such eas-
ily hydrolysable, biodegradable polymers is difficult
(Torrado et  al., 2004). For the unfolding systems, the
mechanical shape memory is relatively short-lived.
Moreover, this kind of dosage form is probably the most
difficult to industrialize and may not be cost-effective.
Finally, expandable systems should not interfere with
gastric motility, must be easily biodegradable, and
must not have sharp edges or cause local damage on
prolonged retention. Permanent retention of such
rigid, large single-unit dosage forms may cause bowel
obstruction, intestinal adhesion, and gastropathy
(Klausner et al., 2003c).
Mucoadhesive or bioadhesive systems
These systems permit a given drug delivery system to
be incorporated with the bio/mucoadhesive agents,
enabling the device to adhere to the stomach (or other
gastrointestinal) walls, thus resisting gastric emptying.
However, the mucus on the walls of the stomach is in a
Floating
delivery system
Expandable system
High density system
Absorption increase through
adsorption window because
drug release occur in stomach
state of constant renewal, resulting in an unpredictable
adherence (Chun et al., 2005).
A bio/mucoadhesive substance is a natural or syn-
thetic polymer capable of adhering to biological mem-
brane (bioadhesive polymer) or the mucus lining of the
GIT (mucoadhesive polymer). Even though some of
these polymers are effective at producing bioadhesion,
it is very difficult to maintain it effectively because of the
rapid turnover of mucus in the GIT (Umamaheshwari
et al., 2004). Furthermore, the stomach content is highly
hydrated; decreasing the bioadhesiveness of polymers,
and it is difficult to target specifically the gastric mucus
with bioadhesive polymers. In addition, the possibility of
esophageal binding might present a challenge regarding
safety aspects (Wang et al., 2000).
Superporous hydrogel
Although these are swellable systems, they differ suffi-
ciently from the conventional types to warrant separate
classification. With pore size ranging between 10 nm to
10 µm, absorption of water by conventional hydrogels
is a very slow process and several hours may be needed
to reach an equilibrium state during which premature
evacuation of the dosage form may occur. Superporous
hydrogels, average pore size > 100 µm, swell to equi-
librium within a minute, due to rapid water uptake by
capillary wetting through numerous interconnected
open pores. Moreover, they swell to a large size and
are intended to have sufficient mechanical strength
to withstand pressure by the gastric contraction (Park
et al., 2005).

Magnetic systems
The magnetic dosage forms contain a small internal
magnet and an extra-corporal magnet that con-
trols the gastrointestinal transit of the dosage form
(Groning et  al., 1998). Although these systems seem
to work, the external magnet must be positioned with
a degree of precision that might compromise patient
compliance.
FDDS
Floating systems, first described by Davis in 1968, are
low-density systems that have sufficient buoyancy to float
over the gastric contents and remain in the stomach for a
prolonged period. While the system floats over the gastric
contents, the drug is released slowly at the desired rate,
which results in increased GRT and reduces fluctuation
in plasma drug concentration (Gangadharappa et  al.,
2007).
Advantages of FDDS
• Improves patient compliance by decreasing dosing
frequency.
• Better therapeutic effect of short half-life drugs can
be achieved.
• Gastric retention time is increased because of
buoyancy.
• Drug releases in a controlled manner for a prolonged
period.
• Site-specific drug delivery to stomach can be
achieved.
• Enhanced absorption of drugs which solubilize only
in the stomach.
• Superior to single unit floating dosage forms as such
microspheres release drug uniformly and there is no
risk of dose dumping.
Limitations of FDDS
• High level of fluids in the stomach is required for
maintaining buoyancy; float efficient working of
dosage form.
• Not feasible for drugs having solubility or stability
problems in gastric fluid.
• Drugs such as nifedipine, which is well absorbed
along the entire GIT and which undergoes significant
first-pass metabolism, may not be desirable candi-
dates for FDDS since the slow gastric emptying may
lead to reduced systemic bioavailability.
• Limitations to the applicability of FDDS for drugs
that are irritating gastric mucosa.
Gastroretentive dosage forms   101
Formulation requirements for FDDS
The device must comply with the following criteria:
• It must have sufficient structure to form a cohesive
gel barrier.
• It must maintain an overall specific gravity lower than
that of gastric contents (1.004–1.010).
• It should dissolve slowly enough to serve as a drug
reservoir.
Classification of FDDS
Floating systems can be classified as effervescent and non-
effervescent 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 (Patel et al., 2005). Gas can be
introduced into the floating chamber by the volatilization
of an organic solvent (e.g. ether or cyclopentane) or by
the CO2 produced as a result of an effervescent reaction
between organic acids and carbonate–bicarbonate salts.
These devices contain a hollow deformable unit that
converts from a collapsed to an expanded position and
returns to the collapsed position after a pre-determined
amount of time to permit the spontaneous ejection of the
inflatable system from the stomach. Figure 2 describes
a multiple-unit oral floating drug delivery system and
explains the working principle of an effervescent floating
drug delivery system.
Effervescent reaction takes
place between acid and
biocarbonate
(B) Drug release from
the floating system
Water enter
into the system
Drug
Matrix of swellable polymers
Organic acids and carbonate-bicarbonate
(A) salts
Figure 2.  (A) Multiple-unit oral floating drug delivery system.
(B) Working principle of effervescent floating drug delivery system.
102   V. K. Pawar et al.
These buoyant systems utilize matrices prepared with
swellable polymers like methocel, polysaccharides like
chitosan, effervescent components like sodium bicarbo-
nate, citric acid and tartaric acid, or chambers containing
a liquid that gasifies at body temperature. The common
approach for preparing these systems involves resin beads
loaded with bicarbonate and coated with ethylcellulose.
The coating, which is insoluble but permeable, allows
permeation of water. Thus, carbon dioxide is released,
causing the beads to float in the stomach.
Strubing et  al. (2008a) investigated the mechanism
of floating and drug release behaviour of poly(vinyl
acetate)-based floating tablets with membrane controlled
drug delivery. Benchtop MRI studies of selected samples
were performed and the results suggested that the drug
release was delayed efficiently within a time interval of
24 h by showing linear drug release characteristics.
Sungthongjeen et al. (2008) designed floating multi-
layer coated tablets based on gas formation using acrylic
polymers (Eudragit RL 30D, RS 30D, NE 30D) and ethyl-
cellulose. The effect of formulation variables on floating
properties and drug release was investigated and the
results showed that an increase in amount of a gas form-
ing agent did not affect the time to float, but increased the
drug release from the floating tablets.
Patel et al. (2007a) used hydroxypropyl methylcellu-
lose, ethyl cellulose, and sodium bicarbonate to prepare
floating tablets and optimization was done using a sim-
plex lattice design. All the tablet formulations remained
buoyant for more than 12 h and the release profile of the
optimized batch fitted best to the zero order model.
Jaimini et al. (2007) prepared floating tablets of famo-
tidine by employing two different grades of methocel
K100 and methocel K15M by effervescent technique. It
was observed that the tablet remained buoyant for 6–10 h
and the drug release from the tablets was sufficiently
sustained.
Shishu et  al. (2007a) developed a FDDS using gas-
forming agents, like sodium bicarbonate, citric acid,
and hydrocolloids, like hydroxypropyl methylcellulose
(HPMC) and Carbopol 934P. The results of the in vitro
release studies showed that the optimized formulation
could sustain drug release for 24 h and remain buoyant
for 16 h.
Nakagawa et al. (2006) developed a novel intra-gastric
FDDS by pulsed plasma-irradiation on the double-
compressed tablet of 5-Fluorouracil as a core material
with outer layer composed of a 68/17/15 weight ratio of
Povidone, Eudragit RL, and sodium bicarbonate, and the
result showed that the release of 5-Fluorouracil from the
tablet was sustained by occurrence of a plasma-induced
cross-link reaction on the outer layer of the tablet
Atyabi et  al. (1996) prepared ion exchange resin
beads loaded with bicarbonate and coated with a semi-
permeable membrane. These prepared beads exhibit
prolonged gastric residence due to the release of carbon
dioxide which is trapped inside the coating of the beads.
Non-effervescent systems
Non-effervescent systems incorporate a high level
(20–75% w/w) of one or more gel-forming, highly swella-
ble, cellulosic hydrocolloids (e.g. hydroxyethyl cellulose,
hydroxypropyl cellulose, hydroxypropyl methylcellulose,
and sodium carboxymethylcellulose), polysaccharides,
or matrix-forming polymers (e.g. polycarbophil, polyacr-
ylates, and polystyrene) into tablets or capsules. On con-
tact with gastric fluid, these gel former polysaccharides
and polymers hydrate and form a colloidal gel barrier
that controls the rate of fluid penetration into the device
and consequent drug release. As the exterior surface of
the dosage form dissolves, the gel layer is maintained by
the hydration of the adjacent hydrocolloid layer. The air
trapped by the swollen polymer lowers the density and
confers buoyancy to the dosage form.
Hydrodynamically balanced systems (HBS) are best
suited for drugs having a better solubility in an acidic
environment and also for the drugs having a specific
site of absorption in the upper part of the small intes-
tine (Rocca et al., 2003). HBS systems can remain in the
stomach for long periods and hence can release the drug
over a prolonged period of time. Hence, the problem of
short gastric residence time encountered with an oral
controlled release formulation can be overcome with
these systems. These systems have a bulk density less
than gastric fluid as a result of which they can float on
the gastric contents. These systems are relatively large in
size and passing from the pyloric opening is prohibited.
These single unit dosage forms contain one
or more gel-forming hydrophilic polymers.
Hydroxypropylmethylcellulose is the most common used
excipient, although hydroxyethylcellulose, hydroxypro-
pylcellulose, sodium carboxymethycellulose, agar, car-
rageenans or alginic acid are also used. The polymer is
mixed with drug and usually administered in a gelatin
capsule. The capsule rapidly dissolves in the gastric fluid,
and swelling of the surface polymers produces a floating
mass. Drug release is controlled by the formation of a
hydrated boundary at the surface. Continuous erosion of
the surface allows water penetration to the inner layers,
maintaining surface hydration and buoyancy.
HBS enjoys several advantages, including ease of
manufacturing and excellent uniformity of matrix
bed. Various in-vivo studies like radiographic (2008)
and gamma scintigraphy (Ali et  al., 2007a; b) have
been done to evaluate in-vivo buoyancy of these sys-
tems. Qureshi, et  al. (2007) prepared a HBS system of
celiprolol hydrochloride using various low density
polymers. Optimization was done on the basis of in
vitro buoyancy and release and the capsule prepared
with Hydroxypropylmethylcellulose K4M and liquid

paraffin gave the best release profile. In another study,
Mendyk et al. (2006) used artificial neural networks as
modeling tools for prediction of various drugs release
patterns from HBS composed with Metholose 90SH
(hydroxypropylmethylcellulose). It was found that arti-
ficial neural networks are capable to accurately predict
release patterns of different drugs from HBS based on
the description of the formulation as well as the chemi-
cal structure of the drug.
The main drawback is the passivity of the operation.
This depends on the air sealed in the dry mass centre
following hydration of the gelatinous surface layer and
hence the characteristics and amount of polymer.
A fluid-filled floating chamber (Zou et  al., 2007)
includes incorporation of a gas-filled floatation cham-
ber into a microporous component that houses a drug
reservoir. Apertures or openings are present along the top
and bottom walls through which the gastrointestinal tract
fluid enters to dissolve the drug. The other two walls in
contact with the fluid are sealed so that the undissolved
drug remains therein. The fluid present could be air,
under partial vacuum or any other suitable gas, liquid, or
solid having an appropriate specific gravity and an inert
behavior. The device is of swallowable size, remains afloat
within the stomach for a prolonged time, and after the
complete release the shell disintegrates, passes off to the
intestine, and is eliminated.
In situ gelling system
Here, gel forming solution swells and forms a viscous
cohesive gel containing entrapped CO2 bubbles on con-
tact with gastric fluid. Formulations also typically contain
antibiotics and antacids. Because in situ gelling systems
produce a layer on the top of gastric fluid, they are often
used for gastroesophageal reflux treatment. Rajinikanth
and Mishra (2008) prepared a floating in situ gelling sys-
tem of clarithromycin to eradicate H. pylori using gellan
as a gelling polymer and calcium carbonate as a floating
agent. The in vivo H. pylori clearance efficiency of the
prepared system and clarithromycin suspension follow-
ing oral administration, to H. pylori infected Mongolian
gerbils was examined by polymerase chain reaction
technique and by a microbial culture method. A floating
in situ gelling system showed a more significant anti-H.
Pylori effect than that of the clarithromycin suspension.
Low-density systems
Low density systems inevitably have a lag time before
floating on the stomach contents, during which the dos-
age form may undergo premature evacuation through the
pyloric sphincter. Low density systems (< 1 g/cm3) with
immediate buoyancy have therefore been developed.
They are made of low-density materials, entrapping oil or
air (Groning et al., 2007). Most are multiple unit systems,
and are also called ‘microballoons’ (hollow microspheres)
Gastroretentive dosage forms   103
because of the low-density core. Microspheres have a
characteristic internal hollow structure and show an
excellent in vitro floatability (Tanwar et al., 2007a). These
microspheres are characteristically free flowing powders
consisting of proteins or synthetic polymers, ideally having
a size less than 200 μm. Microspheres have high loading
capacity (Daharwal et al., 2005) and many polymers have
been used such as albumin, gelatin, starch, polymeth-
acrylate, polyacrylamine, and polyalkylcyanoacrylate.
Solid biodegradable microspheres incorporating a drug
dispersed or dissolved throughout particle matrix have
the potential for controlled release of drugs.
Various types of tablets (bilayered and matrix) are
tested to have floatable characteristics. Some of the poly-
mers used are hydroxypropyl cellulose, hydroxypropyl
methylcellulose, crosspovidone, sodium carboxymethyl
cellulose, ethyl cellulose eudragit RS PO, and eudragit
EPO (Narendra et al., 2006).
The 3-layer principle (Yang et al., 1999) has been used
for the development of an asymmetric configuration drug
delivery system in order to modulate the release extent
and achieve zero-order release kinetics by initially main-
taining a constant area at the diffusing front with subse-
quent dissolution/erosion towards the completion of the
release process.
The effect of formulation and processing variables on
buoyancy and drug release behavior has been studied by
a number of investigators (Shimpi et al., 2004; Wakode
& Bajaj, 2008). Strubing et  al. (2008b) developed float-
ing Kollidon® SR matrix tablets containing Propranolol.
Tablet floating started immediately and continued for
24 h. Floating strength was related to Kollidon® SR level
with improved floating characteristics for samples with
a high polymer/drug ratio. Patel et al. (2007b) and Patel
and Patel (2007) prepared floating granules of ranitidine
HCL using compritol, gelucire 50/13, and gelucire 43/01
as a lipid carrier via melt granulation technique. A full 32
factorial was used for optimization. The results revealed
that the moderate amount of gelucire 43/01 and ethyl
cellulose provides desired release of ranitidine HCL
from the developed floating granules. In another study
they described influence of viscosity of hydroxypro-
pyl methylcellulose, and types of filler on release from
floating matrix tablets using 32 full factorial design. It
was observed that as viscosity of polymer increases, the
release rate constant was decreased. Raval et al. (2007)
developed a matrix controlled drug delivery system
consisting of a poly (styrene-divinyl benzene) copoly-
mer, a matrix-forming polymer, and this highly porous
copolymer provided a low density and, thus, excellent
in vitro floating behavior of the tablets at a concentra-
tion of 15% (w/w). Soppimath et al. (2006) determined
the effect of co-excipients on drug release and floating
property of the hollow microspheres containing nifed-
ipine. Microspheres floated on simulated gastric fluid
104   V. K. Pawar et al.
for more than 12 h and their buoyancy followed the rank
order of: blank (no-coexcipient) > dibutylpathalate >
polyethyleneglycol > poly(έ-caprolactone) after15 h of
floating and the drug was released in a controlled man-
ner. Chauhan et al. (2004) developed risedronate sodium
and Gelucire® 39/01 floating matrices using melt solidi-
fication techniques. Ageing of the matrices was studied
by differential scanning calorimetry, and in vitro drug
release. Ageing causes changes in the crystal structure
of Gelucire®, which is responsible for an increase in drug
release. Dave et al. (2004) investigated the effect of stearic
acid and citric acid on drug release from floating tablets.
The results showed that low amount of citric acid and
high amount of stearic acid favors sustained release of
drug from the system. Iannuccelli et al. (2000) prepared
a floating multiple unit system with solid dispersion
of furosemide with polyvinylpyrrolidone. A decrease
in crystallinity of furosemide was observed by making
solid dispersion; thereby 15-fold or 20-fold increased
both solubility and dissolution of furosemide over that
for untreated furosemide. Durig and Fassihi (2000) devel-
oped swellable hydrocolloid (guar) based matrix tablets
containing verapamil HCl, which were evaluated using
USP dissolution apparatus I and II. Results concluded
that a double mesh device may provide an alternative
to current compendial dissolution methods when the
reliable determination of the true release kinetics of
floating and sticking delivery systems is desired. Krogel
and Bodmeier (1999) developed a multi-functional drug
delivery system based on hydroxypropyl methylcellulose
(HPMC)-matrices (tablets) placed within an imperme-
able polymeric cylinder (open at both ends). The results
showed that the drug release increased with a reduced
HPMC viscosity grade, higher aqueous drug solubility,
decreased HPMC content, and the increased surface area
of the matrix. Rouge et al. (1997) developed hydrophil-
lic mini-matrices filled into hard gelatin capsules which
disperse and float on the contents of the stomach. The
degree of dispersion of the mini-tablets was described
using an equation based on the actual area generated by
the individual or aggregated mini-tablets upon contact
with the dissolution medium. Streubel et al. (2003) pre-
pared floating matrix tablets based on low density foam
powder. The release rate could effectively be modified by
varying the ‘matrix-forming polymer/foam powder’ ratio;
the initial drug loading and the floating behavior of the
low density drug delivery systems could successfully be
combined with an accurate control of the drug release
patterns. Sawicki and Lunio (2005) prepared floating pel-
lets of verapamil hydrochloride as model drug. The best
formulation was evaluated taking into account the effect
of compression force and tablet hardness and friability,
and pellet agglomeration and flotation.
In the last decade, the Emulsification Solvent
Evaporation (Muthusamy et al., 2005; Varshosaz et al.,
2007; Nepal et al., 2007; Choudhury et al., 2008) method
for preparation of low density systems achieved tre-
mendous popularity. Numbers of investigations have
been done employing this particular method, and
floating microspheres (Stithit et  al., 1998; Soppimath
et al., 2001a) were primarily dosage form of choice. The
effect of formulation and process variables such as:
polymer type, drug and polymer ratio, type of solvent,
organic solvents ration, concentration of plasticizer in
aqueous phase, temperature of aqueous phase, stir-
ring rate, time of stirring were evaluated on the yield,
particle size, loading, release, and floating behavior of
microspheres (Leet et  al., 1999; Streubel et  al., 2002;
Sato et  al., 2004). Shape and internal hollow cavity of
floating microspheres were evaluated by SEM and
optical microscopy, and it was found that prepared
systems were perfect spheres with an internal hollow
cavity enclosed by a rigid shell of polymers (Srivastava
et al., 2005; Kale & Tyade, 2007). Some in-vivo studies
suggested that developed formulations remained buoy-
ant over a long period of time in the gastric cavity (Jain
et  al., 2006a) and encapsulated active moiety showed
a high bioavailability (Joseph et  al., 2002; Sato et  al.,
2003). Drug encapsulated in polymer matrix followed
different release patterns like zero order release (Gibley,
2002), Higuchi matrix model, and Pappas Korsmeyer
model (Jain et  al., 2006b). Ionic gelation method, for
preparation of floating beads (Whitehead et  al., 1998;
Talukder & Fassihi, 2004b, Pawar et al., 2008), was also
adopted by a number of investigators. Different classes
of pharmacotherapeutic agents were encapsulated in
these systems, like anti-bacterial agent metronidazole
(Murata et  al., 2000; Sriamornsak et  al., 2005; Ishak
et  al., 2007), anti-cancer agent like 5-fluorouracil
(Shishu et al., 2007b), non-steroidal anti-inflammatory
drug like piroxicam (Lee et al., 2001), anti-hypertensive
agent like verapamil hydrochloride (Sawicki, 2002), and
bronchodilator like theophylline (Yang et al., 2004). In
a study (Gohel & Sarvaiya, 2007) it was revealed that
gastroretentive tablets of rifampicin and isoniazid
minimize the degradation of rifampicin and isoniazid
in acidic medium because the developed system mini-
mized the physical contact between the two drugs and
also controlled release rifampicin in acidic medium.
Gastroretentive systems are gaining more popularity
day-by-day, which can be easily seen by availability of
a number of commercialized gastroretentive products in
the market. From them some are listed in Table 2.
Single and multiparticulate systems of FDDS
Unfortunately, floating devices administered in a single
unit form such as HBS are unreliable in prolonging the
GRT owing to their ‘all or none’ emptying process, and,
thus, they may cause high variability in bioavailability and
 Gastroretentive dosage forms   105

Table 2.  Different marketed product of GRDF.

Product Remarks/type/technology Active ingredient Company
Zanocin OD Effervescent floating system Ofloxacin Ranbaxy, India
Riomet OD Effervescent floating system Metformine HCL Ranbaxy, India
Cifran OD Effervescent floating Form Ciprofloxacin Ranbaxy India
Inon Ace Tablets Foam based floating system Siméthicone Sato Pharma, Japan
Gabapentin GR Polymer-based swelling technology: Gabapentin Depomed, USA
AcuForm™(In phase three clinical trial)
proQuin XR Polymer-based swelling technology: Ciprofloxacin Depomed, USA
AcuForm™
Glumetza Polymer-based swelling technology: Metformin HCL Depomed, USA
AcuForm™
Metformin GR ™
Polymer-based swelling technology: Metformin HCL Depomed, USA
AcuForm™
Kadian — Morphine sulfate Sumitomo Pharma, Japan
Prazopress XL Effervescent and swelling-based Prazosin HCl Sun Pharma, Japan
floating system
Metformin Hcl LP Minextab Floating® Metformin HCL Galenix, France
Cafeclor LP Minextab Floating® Cefaclor Galenix, France
Tramadol LP Minextab Floating® Tramadol Galenix, France
Cipro XR Erodible matrix based system Ciprofloxacin hydrochloride Bayer, USA
and betaine
Accordion Pill TM Expandable film filled in capsule — Intec Pharma
Baclofen GRS Coated multi-layer floating & swelling Baclofen Sun Pharma, India
system
Coreg CR Gastro retention with osmotic system Carvedilol Glaxosmithkline
Madopar Floating, CR capsule Levodopa and Benserzide Roche, UK
Liquid gaviscon Effervescent floating liquid alginate Alginic acid and Sodium Reckitt Benckiser Healthcare, UK
preparation bicarbonate
Valrelease Floating capsule Diazepam Roche, UK
Cytotec Bilayer floating capsule Misoprostol (100mcg/200mcg) Pharmacia Limited, UK
Topalkan Floating liquid alginate Aluminum magnesium antacid Pierre Fabre Medicament, France
Conviron Colloidal gel forming FDDS Ferrous sulfate Ranbaxy, India
Almagate flatcoat Floating liquid form Antacid —

local irritation due to the large amount of drug delivered
at particular sites of GIT (Singh & Kim, 2000). In contrast,
multiple unit particulate doses forms (e.g. microspheres)
have the advantages that they pass uniformly through the
GIT to avoid the vagaries of gastric emptying and provide
an adjustable release, thereby reducing the inter-subject
variability in absorption and risk of local irritation. At
present, hollow microspheres are considered to be one
of the most promising buoyant systems as they combine
the advantages of multiple systems with good floating
properties.
Current trends and advancements
Dual working systems
These systems are based on the two working princi-
ples of either floating and bioadhesion or swelling and
bioadhesion. FDDS are formulated to persist floating
on the gastric fluid when the stomach is full after a
meal. However, as the stomach empties and the tablet
reaches the pylorus, the buoyancy of the dosage form
may be reduced. It may be that the dosage form will
then pass through the pylorus into the small intestine.
Thus, the buoyancy of an FDDS in the stomach may
be limited to only 3–4 h. Furthermore, floating systems
do not always release the drug at the intended site. In
a bioadhesive drug delivery system, it is quite likely
that the system becomes dislodged from the stomach
mucosa wall when the system is full and the semi-
liquid contents are churning around due to the effect
of peristalsis. A dual working system would overcome
drawbacks associated with bioadhesive, swelling,
and floating systems, and would have a significant
effect on improving the therapeutic effect of the drug
involved. Sonar et  al. (2007) developed a bilayer and
floating-bioadhesive drug delivery system exhibiting a
unique combination of floatation and bioadhesion to
prolong residence in the stomach using rosiglitazone
maleate as a model drug. The release of rosiglitazone
maleate from the tablets followed the matrix first-order
release model. The tablet was buoyant for up to 8 h in
the human stomach. Varshosaz et al. (2006) prepared
106   V. K. Pawar et al.
floating-bioadhesive tablets of ciprofloxacin using
sodium carboxymethylcellulose, polyacrylic acid, cit-
ric acid, and sodium bicarbonate. All the tablets were
floated for more than 23–24 h and increasing sodium
carboxymethylcellulose caused higher mucoadhesion
than polyacrylic acid. Zheng et  al. (2006) developed
floating-bioadhesive microparticles of clarithromycin
for the eradication of H. pylori using ethylcellulose
and chitosan. In vivo mucoadhesion testing showed
that 61% of the microparticles could be retained in the
stomach for 4 h. Chavanpatil et  al. (2006) developed
a swellable and bioadhesive formulation of ofloxacin
using psyllium husk, hydroxypropylmethylcellulose,
and crosspovidone. The swelling property was increased
with the increasing concentration of crosspovidone.
The bioadhesive property of the developed formulation
was found to be significantly increasing in combina-
tion as compared to the hydroxypropylmethylcellulose
and psyllium husk alone. Umamaheshwari et al. (2002;
2003) developed floating-bioadhesive dosage forms of
acetohydroxamic acid coated with cellulose acetate
butyrate. The cellulose acetate butyrate coated dosage
form showed higher buoyancy time than uncoated
resin particles, but the amount of cellulose acetate
butyrate coated microcapsules that remained in the
stomach was slightly lower than that of uncoated resin
particles. Results of in vitro growth inhibition studies
suggested a better inhibition rate than the plain aceto-
hydroxamic acid.
Floating osmotic systems
A floating osmotic drug delivery system employs the
principal of osmotic pressure to float on the gastric
fluid. Basically these systems comprise of three parts;
an osmotic core (containing drug reservoir, osmotic
agents, and other excipients), a shape retaining semi-
permeable membrane; and an outer compression
coating consisting of gas generating and gel forming
agents. For delivery of drug an orifice is bored through
both the outer layers. After administration when this
system comes in contact with gastric fluid, initially CO2
is generated due to the presence of a gas forming agent
and this generated gas entraps within the bed of swelled
gel, thus the system became buoyant due to diminished
density. Delivery of drug then totally depends upon the
osmotic pressure generated inside the osmotic core.
First a saturated solution of drug is formed due to the
flow of fluid through the semi-permeable membrane
and second expulsion of drug through the orifice due
to osmotic pressure develops within the osmotic core.
A major advantage of floating osmotic drug delivery
systems is that they deliver drug independent to physi-
ological parameters like pH of gastric fluid (Kumar et al.,
2008).
Floating-pulsatile systems
Pulsatile drug delivery systems release the drug
rapidly and completely after certain lag times. However,
an uncertainty is always associated with such systems,
they may expel out from the body without releasing
drug content due to the presence of lag time. Floating
pulsatile systems develop to overcome this drawback and
have gained increasing interest during recent years for
a number of drug therapies. In a study Zou et al. (2008)
developed a floating-pulsatile drug delivery system of
verapamil HCL. The dry-coated tablet consists of a drug-
containing core coated with a hydrophilic erodible poly-
mer followed by a buoyant layer, prepared with Methocel
K4M, carbopol 934P, and sodium bicarbonate. Developed
formulations were evaluated for their buoyancy and a
dissolution, pharmacokinetic, and gamma-scintigraphic
study was also done. Results showed that the prepared
system remained in gastric fluid and gave rise to control-
led release of drug. Badve et al. (2007) developed hollow
calcium pectinate beads for floating-pulsatile release of
diclofenac sodium. The floating beads obtained were
porous (34% porosity), hollow with bulk density < 1, and
had a floating time of 14–24 h. In vivo studies by gamma
scintigraphy determined on rabbits showed gastroreten-
tion of beads up to 5 h.
In-vivo methods of evaluation of GRDF (Parikh
& Amin, 2008)
γ-Scintigraphy
γ-Scintigraphy can be use to evaluate in-vivo buoyancy
and in-vivo release performance of different type of
GRDF. In this technology a stable radioisotope like 111In
is formulated within the developed system and admin-
istered in healthy human volunteers (Goole et al., 2008).
Major drawbacks with such a technique are associated
ionization radiations, limited topographic information,
low resolution, and complicated and expensive prepara-
tion of radiopharmaceuticals (Wilding et al., 2001).
Radiology
This method includes pre-clinical estimation of gastrore-
tention. In comparison to γ-scintigraphy, radiology is a
more simple and cost effective technique. However, limi-
tations regarding exposure to X-rays decline its popular-
ity because for optimum evaluation of buoyancy a high
amount of contrasting agent (BaSo4) is generally required
(Tanwar et  al., 2007b). Radiographs were taken after
ingestion of the dosage form, to locate the floating and
non-floating (fabricated) dosage forms at various peri-
odic time intervals (Iannuccelli et al., 1998; Baumgartner,
et al., 2000; Klausner et al., 2003a).

Gastroscopy
This is considered a minimally invasive procedure since
it does not require an incision into one of the major body
cavities. This technique involves visual inspection of
GRDF in the stomach (Klausner et al., 2003b). Basically
it is a type of peroral endoscopy which comprises optic-
fibers and a video camera. For more detailed information
the evaluated system can be drawn out from the stomach.
However, on the other hand the quality of study and its
interpretation are highly dependent on the expertise of
the endoscopist. Active uncontrolled bleeding, retained
blood in the stomach, and retained food or antacids may
also lead to an inadequate study.
Ultrasonography
Ultrasonic waves are used to produce images of body
structures. The waves travel through tissues and are
reflected back where density differs. The reflected
echoes are received by an electronic apparatus that
measures their intensity level and the position of the
tissue reflecting them. The results can be displayed as
still images or as a moving picture of the inside of the
body (Hendee, 1994). Most dosage forms do not have
sharp acoustic mismatches across their interface with
the physiological milieu. Therefore, ultrasonography
is not routinely used for the evaluation of FDDS. The
characterization included assessment of intra-gastric
location of the hydrogels, solvent penetration into the
gel, and interactions between the gastric wall and FDDS
during peristalsis.
Magnetic resonance imagining (MRI)
MRI is a non-invasive diagnostic technology. MRI uses
a powerful magnetic field, radio frequency pulses, and
a computer to produce detailed pictures of organs,
soft tissues, bone, and virtually all other internal body
structures. The images can then be examined on a com-
puter monitor, transmitted electronically, and printed
or copied to a CD. MRI does not use ionizing radiation
(x-rays). In the last couple of years, MRI was shown to
be a valuable tool in gastrointestinal research for the
analysis of gastric emptying, motility, and intra-gastric
distribution of macronutrients and drug models. The
advantages of MRI include high soft tissue contrast,
high temporal and spatial resolution, as well as a lack
of ionizing irradiation. Also, harmless paramagnetic
and supra-magnetic MR imaging contrast agents can
be applied to specifically enhance or suppress signal
of fluids and tissues of interest and thus permit bet-
ter delineation and study of organs (Dorozynski et al.,
2007).
Gastroretentive dosage forms   107
Conclusion
Increased GRT of a controlled release system has great
practical applications. A controlled release system with
gastroretentive ability can significantly improve bioavail-
ability and improve the efficiency of medical treatment.
These systems also meliorate the efficacy of drugs which
have altered stability, solubility, and absorption in GIT.
All the gastroretentive systems have their positive aspects
and drawbacks. Concerning this floating drug delivery
system based on effervescent and non-effervescent
systems for modulation of oral controlled drug delivery
was found to be of great importance. These systems
have special additional advantages for the drugs that
are primarily absorbed from the upper segment of the
GIT. It is also evident that the maximum number of com-
mercial products and patents of gastroretentive systems
belong to the class of floating drug delivery systems. So,
with an improved knowledge of formulation aspects and
physiochemical and pharmacological prospects of drugs
someone can design an optimum system for drug deliv-
ery in the gastric cavity.
Declaration of interest
The author reports no declaration of interest.
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