Turk J Pharm Sci 2022;19(4):476-487

DOI: 10.4274/tjps.galenos.2021.44959 REVIEW

Features and Facts of a Gastroretentive Drug

Delivery System-A Review
Kuldeep VINCHURKAR1,2*, Jitendra SAINY2, Masheer Ahmed KHAN2, Sheetal MANE2, Dinesh K MISHRA1, Pankaj DIXIT1

1Indore Institute of Pharmacy, Department of Pharmaceutics, Indore, India

2Devi Ahilya Vishwavidyalaya University, School of Pharmacy, Department of Pharmaceutics, Indore, India

ABSTRACT

English oral delivery of drug was the commonly used modality because of patient compliance and ease of administration. After oral administration of
any drug, its bioavailability is affected by its residence time in stomach. Recently, gastroretentive drug delivery systems (GRDDS) have gained wide
acceptance for drugs with a narrow absorption window, decreased stability at high alkaline pH, and increased solubility at low pH. This approach
develops a drug delivery system, which gets retained within gastric fluid, thereby releasing its active principles in the stomach. Some methods
used to achieve gastric retention of drugs include the use of effervescence agents, mucoadhesive polymers, magnetic material, bouncy enhancing
excipient, and techniques that form plug-like devices that resist gastric emptying. This review provides a concise account of various attributes of
recently developed approaches for GRDDS.
Key words: Bioavailability, bio/mucoadhesive system, therapeutic window, gastric emptying

INTRODUCTION Some of the common advantages associated with use of GRDDS

Oral administration is popular despite continuous improvement include improved patient compliance by reducing the frequency
in drug delivery approaches owing to patient comfort and ease of dosing; improved therapeutic efficacy of drugs with a short
of administration. Controlled release drug delivery systems are half-life; site-specific delivery of medications; sustained and
designed for oral administration. These drug delivery systems controlled release of drugs in the stomach; enhanced residence
time of drugs at the absorption site; improved bioavailability
release the medication in a predetermined, predictable, and
from the gastrointestinal tract; avoiding dose dumping of
controlled way. They are not suitable for drugs with low
medicines.6
bioavailability due to stability or absorption issues.1 These
problems can get better through modern approaches, which To develop GRDDS, different materials like ion-exchange
resins, mucoadhesives, high-density materials, raft forming
are designed to increase the residence of such drugs in the
substances, magnetic substances, and super porous hydrogels
stomach for an extended time. Such drug delivery systems
are used.7,8
are called gastroretentive drug delivery systems (GRDDS).
GRDDS are suitable for those drugs, which are absorbed from This review provides a concise account of various attributes of
recently developed approaches for GRDDS.
the stomach (e.g. albuterol),2 labile at alkaline pH (e.g. ranitidine
and metformin),3 poorly soluble at alkaline pH (e.g. furosemide Anatomy and physiology of the stomach
and diazepam),4 and having a narrow window of absorption (e.g. Knowledge about the anatomy and physiology of the stomach
riboflavin and levodopa).5 is essential for the successful formulation of gastroretentive

*Correspondence: kuldeepvinchurkar@gmail.com, Phone: +917387527076, ORCID-ID: orcid.org/0000-0002-9206-9587

Received: 10.03.2021, Accepted: 18.06.2021
©Turk J Pharm Sci, Published by Galenos Publishing House.

476
 VINCHURKAR et al. Gastroretentive Drug Delivery System 477

dosage forms. Anatomically, the stomach is divided into three gastric residence of the formulation. A high-calorie meal
areas: the proximal portion toward the esophagus is fundus, containing proteins, fats, and fibrous compounds increases
followed by the body, which serves as a storage site for gastric retention time. In the case of multiple meals, the gastric
engulfed food, and the antrum, last part that connects the body retention is more than a single meal due to persistent inhibition
to the small intestine. Antrum helps in churning action and in of peristalsis.
gastric emptying.9 In fasting state, a sequence of contractions Also, some other factors, such as sex and age, affect gastric
occurs cyclically through the stomach and intestine every 120- retention. Compared with males, females have a slower gastric
180 min, called the migrating myoelectric cycle. It is further emptying time irrespective of height, weight, and body surface.
divided into four phases. The pattern of contraction changes A person at the age of more than 70 exhibits longer GRT. In
in a fed state is termed as the digestive motility pattern.10 This comparison, neonates show less GRT compared with geriatric
pattern comprises phase 1- (basal phase); phase 2- (preburst patients.13-15
phase); phase 3- (burst phase); and phase 4.11 Figure 1 depicts
the motility pattern in the gastrointestinal tract. Gastroretentive dosage form approaches
Continuous research and advancements in various approaches
Physicochemical properties of GRDDS to gastroretentive dosage forms over the last few years are
Physicochemical properties of GRDDS include density, size, as presented in Figure 2. These approaches to GRDDS help in
and shape of the dosage form, which play major roles in the delivering the medicament in a sustained and restrained way
formulation of GRDDS. The dosage forms having a density through the gastrointestinal tract.
lower than the gastric contents can float to the surface, while
high-density systems sink to the bottom of the stomach. For an Classification of GRDDS
ideal formulation, the density should be in the range of 1.0-2.5 GRDDS are classified into mainly two types: floating and non-
g/cm3. Dosage forms having a diameter of more than 7.5 mm floating systems. Floating systems are further classified into
show better gastric residence time (GRT). Circular, spherical effervescent system and non-effervescent systems based
or tetrahedron-shaped devices show excellent gastroretentive on the mechanism of floating, while non-floating systems
properties.12 classified into four different classes based on the mechanism
used for gastroretention. Figure 3 depicts the classification of
Physiological factors affecting retention of GRDDS in the the GRDDS.
stomach
The most important factors controlling the gastric retention I- High-density system
time of dosage forms include fed or unfed state, nature of The density of dosage form plays an important factor in the
the meal, caloric content, and frequency of feeding. In the formulation of the GRDDS. A high-density system uses its
case of a fasting environment, gastric retention time is less weight as a retention mechanism. To enhance the gastric
due to the increase in GI motility. Emptying of gastric content residence of a drug in the stomach, its density must exceed
occurs due to peristalsis. If peristalsis coincides with dosage the normal stomach content (1.004 g/mL).16 Figure 4A depicts
form administration, the gastric residence is short. However, the principle of a high-density system. Clarke et al.17 compared
after meals, peristalsis is delayed and may help increase the

Figure 1. Motility pattern in gastrointestinal tract Figure 2. Approaches of gastroretentive drug delivery system
478 VINCHURKAR et al. Gastroretentive Drug Delivery System

gastrointestinal transit of placebo pellet systems of varying systems remain buoyant due to lower density and provide
densities using gamma scintigraphy. They reported that GRT continuous drug release. In this way, they increase GRT of
of such a formulation can be extended from an average of 5.8 the drug and improve its bioavailability.18 Figure 4B depicts the
h to 25 h, depending more on density than on the diameter of principle of floating or low-density systems.
the pellets. (A) Effervescent system
II- Floating or low-density system This system uses carbonates (e.g. sodium bicarbonate) to
Another approach to increase gastric residence is to lower the generate in situ carbon dioxide (CO2).19,20 Organic acids (e.g.
citric and tartaric acids) are added to speed up the reaction, thus
density of dosage form than the normal gastric content. These
reducing the density of dosage form and remaining buoyant in
the stomach.20 It is categorized into two classes:
a) Volatile liquid/vacuum type: These are further classified into
three types.
i) Inflatable system
It consists of a pullout system having a space filled with volatile
liquids that evaporate at body temperature. Thus, when these
systems are introduced into the stomach, the chamber inflates,
and the system floats. The inflatable chamber comprises a
bioerodible polymer filament that is made from polymers like
polyvinyl alcohol and polyethylene. When the inflatable chamber
floats in the gastrointestinal fluid, the polymer gradually
dissolves and releases the drug. After some time, due to
polymer dissolution, the inflatable section collapses.19,20 Figure
4C depicts a floating effervescent type of inflatable system.
ii) Intragastric floating system
It contains a chamber filled with a vacuum and includes a
microporous compartment serving as a drug reservoir.20 Figure
5 depicts a floating type of intragastric system. Patel et al.21
developed intragastric floating tablets of verapamil HCl using
hydroxypropyl methylcellulose (HPMC), carbopol, and xanthan

Figure 5. Intragastric floating gastrointestinal drug delivery system.

Figure 3. Classification of gastroretentive drug delivery system

Figure 4. Different types of gastroretentive drug delivery system. A) High density system, B) floating/low density system, C) inflatable system, D)
mucoadhesive system, E) magnetic system (i- stomach, ii- gastric fluid, iii- dosage form)
 VINCHURKAR et al. Gastroretentive Drug Delivery System 479

gum as gel-forming agents. Buoyancy was achieved by adding increase the overall bioavailability of the drug. They developed
an effervescent mixture of sodium bicarbonate and anhydrous drug-containing core units using the direct compression
citric acid. Optimized formulation exhibited satisfactory results process, which were coated with three successive layers of an
with a short buoyancy lag time of 36 sec, a total buoyancy time inner seal coat, effervescent layer (sodium bicarbonate), and an
of more than 24 h, and controlled drug release for up to 24 h. outer gas-entrapped polymeric membrane of polymethacrylates
(eudragit RL30D, RS30D, and combinations of them). They found
iii) Intragastric-osmotically controlled system
that increasing the coating level of gas-entrapped polymeric
Osmotic control can be achieved using a biodegradable capsule membrane decreased the drug release.
comprising inflatable floating support congestion with an
osmotic pressure-controlled drug delivery device.22,23 Zhao et iii) Floating systems with ion exchange resins
al.24 used fenofibrate-loaded mesoporous silica nanoparticles These floating systems are mainly developed to prolong the GRT
to prepare an oral push-pull osmotic pump. Polyethylene oxide of dosage forms using ion exchange resin. They consist of drug
(100,000) and polyethylene oxide (6,000,000) were selected resin complex beads loaded with bicarbonate ions, and they are
as suspending agents and expanding agents, respectively. coated with hydrophilic polymers.30 It results in the generation
Cellulose acetate was used as a semipermeable membrane of CO2 gas when it comes in contact with the gastric fluid and
along with polyethylene glycol 6,000 to increase flexibility and causes the beads to float. Atyabi et al.31 developed a floating
control the membrane permeability. The prepared system is system based on an ion exchange resin, which consists of resin
reported to stay in the stomach for a period of 21.72 h rather beads, loaded with bicarbonate and a negatively charged drug
than 12.48 h of the reference tablet and delivers the drug in an that was bound to the resin. Two resins, i.e. Amberlite IRA-400
approximately zero-order manner for 24 h. and Dowex 2 x 10, were investigated and both exhibited in vitro
b) Matrix tablets: They are of two types, i.e. single-layer and floating times of over 24 h using a standardized procedure. The
bilayer matrix tablets. The single-layer matrix tablets are coated dosage form remained for over 3 h in the stomach with
prepared using a drug and a hydrocolloid forming gel, while the non-coated system and demonstrated a marked increase in
the bilayer matrix tablet contains one immediate-release layer retention over conventional formulation.
and another sustained release layer. Saisivam et al.25 developed (B) Non-effervescent systems
single-layer floating matrix tablets of losartan potassium
In non-effervescent floating systems, the drug comes in
using different proportions of HPMC-K4M and karaya gum as
contact with gastric fluid and it swells. It maintains its shape,
retarding polymer and sodium bicarbonate as an effervescent
and its density remains less than one, hence it floats in gastric
agent by direct compression method. Results of an in vivo study
juice.32 Matrix forming polymer, gel-forming, or swellable type
of optimized formulation displayed the floatability of tablet in
hydrocolloids are used for these types of floating systems.
gastric content and prolonged the GRT to approximately 12 h.
They are further classified as follows:
X-ray imaging study in albino rabbits indicated the residence of
tablet in the stomach even after a period of 12 h. i. Hydrodynamically balanced systems (HBS)
These systems mainly consist of a mixture of drugs and
c) Gas generating systems: Gas-generating systems are
hydrocolloids that forms a gelatinous barrier, when it comes in
prepared using effervescent compounds along with hydrophilic
contact with gastric fluid due to swelling of the combination. It
polymers.
remains buoyant in the stomach for an extended period as its
i) Floating capsules bulk density is less than one in gastric fluid. Nayak and Malakar33
These dosage forms involve encapsulation of drugs in developed gastroretentive theophylline HBS capsules using
hydrophilic polymers like ethyl cellulose and eudragit RS-100 HPMC, polyethylene oxide, polyvinylpyrrolidone, ethylcellulose,
with effervescent agents such as sodium bicarbonate, calcium liquid paraffin, and lactose to control the delivery of theophylline
carbonate, etc. Moursy et al.26 developed a hydrodynamically for a longer period in the stomach with a minimum floating time
balanced capsule containing a mixture of nicardipine of 6 h.
hydrochloride and hydrocolloids. Upon contact with gastric
ii. Microballoons
fluid, the capsule shell dissolves with subsequent swelling,
Microballoons are described by the gradual addition of drug-
forming a gelatinous barrier, which remains buoyant in the
containing emulsion into a volatile solvent. On evaporation of the
gastric juice for an extended period.
solvent, gas is generated in a dispersed polymer droplet, which
ii) Floating pills results in the formation of an interior orifice in the microsphere
Multiple unit types of oral floating dosage forms have been of the drug with polymer. It is also called emulsion solvent
developed using a hydrophilic polymer in the outer layer and an diffusion method.22 The floating time of microspheres depends
effervescent agent in the inner layer. When it comes in contact upon the type and amount of polymer used in the formulation.
with the gastric fluid, the outer layer of hydrophilic polymer Gupta et al.34 developed pantoprazole sodium-loaded
starts to swell and then sinks, but as the effervescent agent microspheres using eudragit L100 by adopting an emulsion
meets gastric content, it releases CO2, and the system starts to solvent diffusion method with a non-effervescent approach.
float.27,28 Meka et al.29 prepared multiple-unit minitab of captopril The results of in vitro and in vivo studies exhibited a suitable
based on a gas formation technique to prolong the GRT and to drug-release pattern in terms of increased bioavailability and
480 VINCHURKAR et al. Gastroretentive Drug Delivery System

efficient ulcer healing effect. Figure 6 depicts the steps involved tablets of pregabalin once a day using wet granulation and
in the preparation of microballoons by solvent diffusion method. compaction. They found that the amounts of HPMC and
crospovidone were found be critical factors affecting in vitro
iii. Alginate beads
dissolution and floating properties of the prepared tablets.
These systems are prepared using a hydrocolloid gel-forming Figure 7 depicts a schematic of single-layered floating tablets.
agent and sodium alginate as the interlocking agents. In the
b. Double-layered floating tablets: It comprises of two
presence of gastric fluid, the hydrocolloid absorbs water and
formulations separated by layering, one on top of the other,
forms a barrier that results in entrapment of air in the polymer,
having two different release profiles.3,38 Kuldeep et al.39
which causes swelling of the polymer, and hence the dosage
developed a bilayer floating tablet of metoprolol succinate
form starts to float, and results in releasing the drug for a
(sustained-release layer) and rosuvastatin calcium (immediate-
prolonged period. Ghareeb and Radhi35 developed trimetazidine
release layer) by direct compression method. HPMC K100,
calcium alginate floating beads using sodium alginate solution
K4M, and K15M were used as gel-forming agents, while cross
(2, 3, and 4% w/v), HPMC, and peppermint oil (15, 20, and
carmellose sodium, sodium starch glycolate, and crospovidone
25% v/v) using emulsion gelation method. They found that oil
were used as super disintegrant. Sodium bicarbonate is used
entrapped floating beads gave promising results for sustaining
as an effervescent agent. From the in vitro buoyancy study,
the release of the drug over 10 h. it was observed that as the concentration of gas-generating
iv. Layered tablets agents increases, floating lag time decreases. Also, the polymer
Layered tablets are more popular due to ease of their gas generating agent ratio was found to influence the floating
preparation, low cost, and high stability. lag time and the total duration of floating.
a. Single-layered floating tablets: These tablets were developed III- Mucoadhesive and bioadhesive systems
by mixing drug and gas generating agents within the matrix A mucoadhesive and bioadhesive system uses its adhesive
tablet. These formulations have lower bulk density than gastric properties to target a drug to a specific region of the body for
fluid, and thus they remain buoyant in the stomach by increasing an extended period. Figure 4D displays a mucoadhesive system
GRT.36 Kim et al.37 developed non-effervescent gastroretentive of GRDDS. For this, bioadhesive or mucoadhesive polymers

Figure 6. Preparation technique and mechanism of microballoons formation

Figure 7. Mechanism of single layer tablet

 VINCHURKAR et al. Gastroretentive Drug Delivery System 481

are mainly used.40 Natural polymers such as sodium alginate, formulation with a small internal magnet is controlled. Several
gelatin, guar gum, etc., and semisynthetic polymers such as reports tell about the positive results of this system, but the
HPMC, lectins, carbopol, and sodium carboxymethyl cellulose success of this system depends upon the selection of the
are widely used for mucoadhesion. The adhesion is mediated magnet position with very high precision.48 Gröning et al.49
by hydration, bonding, or receptor interactions.41,42 Madgulkar developed peroral acyclovir depot tablets with an internal
et al.43 developed sustained-release tablets of itraconazole magnet. An extracorporeal magnet was used to prolong the GRT
using mucoadhesive polymer carbopol 934P and HPMC K4M. of the dosage form and to influence the duration of absorption
They confirmed sustained drug release and gastric retention of acyclovir. They performed an in vivo study with five healthy
for six hours in albino rats. Figure 8 depicts the principle of male subjects and determined the plasma concentration-time
mucoadhesive drug delivery systems. profiles of acyclovir. Computer simulations were carried out to
display the influence of GRT of acyclovir depot preparations on
IV- Swelling system
the plasma concentration-time profiles of acyclovir. Figure 4E
These systems, when come in contact with gastric fluid, their displays a magnetic system of GRDDS.
size increases significantly than that of the pyloric sphincter
and thus, after swelling, remain logged in the stomach. These In vitro assessment
are also called a “plug type system”.44 Controlled and sustained For GRDDS, in vitro assessment is very essential to predict
drug release is achieved using an appropriate excipient. The gastric transit behavior. Following are the parameters, which
swelling ability of polymer mainly depends upon the degree of should be considered for designing novel gastroretentive
cross-linking of hydrophilic polymer network. The high degree formulations.
of cross-linking maintains the integrity of the system, while a i. Buoyancy lag time
low degree of cross-linking causes extensive swelling resulting
It is the time taken for gastroretentive formulations to move
in rapid dissolution of the polymer.45
onto the surface of the dissolution medium. It is determined
V- Superporous hydrogels using a USP dissolution apparatus containing 900 mL of 0.1 N
Superporous hydrogels are a three-dimensional network of HCl solution as a testing medium maintained at 37°C. The time
hydrophilic polymers that have numerous super-size pores required to float different dosage forms noted as floating lag
inside them. The swelling of superporous hydrogels occurs time.50
by the mechanism of capillary wetting through interconnected ii. Floating time
open pores. To develop superporous hydrogels, certain
This determines the buoyancy of dosage form. In this test, a
ingredients like initiators and cross-linkers are used to initiate
specific dissolution apparatus is used depending upon the type
the cross-linking.46 Other ingredients were foam stabilizers,
of dosage form with 900 mL of dissolution medium kept at
foaming aids, and foaming agents. Desu et al.47 developed
37°C. The floating time or floating duration of the dosage form
a superporous hydrogel system using N’, N’-methylene
is determined by visual observation.51,52
bisacrylamide as the cross-linking operator and polyvinyl
alcohol as a composite specialist, ammonium persulfate and iii. Specific gravity/density
N, N-tetramethylenediamine as an initiator pair and Span 80 Specific gravity estimates are essential for both low-density
as a surfactant. They are used as a froth stabilizer to make a and high-density GRDDS. Specific gravity is determined using
permeable structure using the gas-forming method. the displacement method.53
VI- Magnetic system iv. Swelling index
In this system, by using a strong magnet with a powerful magnetic Swelling index is determined by immersing the tablets in 0.1
field onto the body surface, the movement of gastroretentive N HCl at 37°C and their periodic removal at regular intervals.54

Figure 8. Principle of mucoadhesive drug delivery system

482 VINCHURKAR et al. Gastroretentive Drug Delivery System

v. Water uptake viii. In vitro dissolution tests

In this study, the dosage form is removed from the dissolution This test is performed to determine drug release from GRDDS in
medium after the regular interval and a weight change is gastric fluid and intestinal fluid maintained at 37°C at a definite
determined.55 time using USP dissolution type II apparatus (paddle).59,60
Water uptake (WU) = (Wt - Wo) * 100/Wo Here, after in vitro assesment, Table 1 represents the recent
trends in GRDDS, while Table 2 represents the names of drug
where Wt= weight of the dosage form at time t, Wo= initial weight candidates for GRDDS.
of the dosage form
Evaluation of microsphere and beads
vi. Weight variation An optical microscope was used to measure the particle size
Various official methods are recommended by pharmacopeias of beads and microspheres. Surface morphology and cross-
to calculate the weight variation. Usually, the individual and sectional morphology are evaluated with the help of a scanning
average weight of 20 tablets are recorded. From these data, electron microscope.
average weight and weight variation is calculated.56,57
In vivo assessment
iii. Hardness and friability a. Radiology
Hardness or crushing strength is determined using a Monsanto This technique is mainly used to determine the position of
tester, Strong cobb tester, Pfizer tester, etc. Friability (strength) gastroretentive dosage form filled with barium sulfate (radio-
of tablets is determined using a Roche friabilator.58,59 opaque marker) inside the body system concerning time using

Table 1. Showing some recent trends in GRDDS

Drug Requirements for development Dosage forms References

a) Low solubility
Osmotic tablet
Diltiazem HCl b) Short half-life 63
(pump)
c) Low bioavailability (40-50%)

a) Short half-life
Theophylline Floating capsule 64
b) Low bioavailability

a) Short half-life
Metformin HCl Beads 65
b) Low bioavailability

Ciprofloxacin a) Low bioavailability

CR floating tablet 66
hydrochloride b) Short elimination half-life

a) Short half-life
b) Oral bioavailability is poor (15-30%) due to poor
Acyclovir SR floating microsphere 67
water solubility
c) Degrade at high pH

a) Short half-life
Floating (pulsatile)
Ranitidine HCl b) Absorption window in a part of GIT 68
DDS
c) Poor bioavailability

a) Short elimination half-life (about 4 h)

b) Narrow absorption window and absorbed in
Ciprofloxacin HCl Floating tablet (matrix) 69
proximal SI
c) Freely soluble in water

a) Dose dependant solubility

Ziduvudine b) Short biological half-life Tablet 72
c) Poor bioavailability

a) Acidic drug
Cephalexin b) Short half-life Floating tablet 73
c) Poor bioavailability
GRDDS: Gastroretentive drug delivery systems
 VINCHURKAR et al. Gastroretentive Drug Delivery System 483

X-ray. X-ray pictures are taken at different intervals to record optical, tubular, and slender instrument called “endoscope” is
the correct position of the dosage form.61,62 used to look deep inside the body parts such as the stomach,
esophagus, and small intestine.65,66
b. Scintigraphy
Similar to radiology, it is used to determine in vivo floating d. Ultrasonography
behavior of the gastroretentive dosage form. In scintigraphy, It is a diagnostic imaging technique, in which ultrasound is used
99mTc pertechnetate is used as an emitting material instead of for imaging internal body structures. The main disadvantage of
an X-ray to engulf the formulation to record the image.63,64 this test is non-detectability at entrails.1,66,67

c. Gastroscopy e. 13C octanoic acid breath test

Gastroscopy is widely used for visual examinations of Radioactive 13C octanoic acid is used to assess the extent of
gastroretentive dosage forms. In this technique, an illuminate absorption of drugs from GRDDS. This compound gets absorbed
Table 2. Some of the drug candidates for GRDDS
Pharmacological
Stability in gastric Absorption and oral
Drug and/or therapeutic Solubility Half-life (h) References
and intestinal bioavailability
class
70-80% absolute
Itraconazole Antibiotics Low water solubility - 4 66
bioavailability
Slightly soluble in
Acyclovir Antiviral - Rapidly absorbed 3.0 ± 1.4 67
water
Histamine H2- Low solubility at 50% absolute
Ranitidine Colonic metabolism 2.5-3 68
receptor antagonist alkaline Ph bioavailability
Mainly absorbed in
Ciprofloxacin Fluoroquinoline Freely soluble in water - 4 69
proximal areas
Mainly absorbed from
Furosemide Loop diuretic Poor water solubility - 1.3 ± 0.8 70
stomach
Tacrolimus Immunosuppressant Poor water solubility - Low oral availability - 71
Angiotensin Stable at gastric
Captopril converting enzyme Freely soluble in water pH but unstable in - 2 72
inhibitor intestine
Oral hypoglycemic
Repaglinide Poorly soluble in water - Low bioavailability 1 73
agent
Metformin Absolute bioavailability
Antidiabetic Freely soluble in water - 1.5-1.6 74
hydrochloride (50-60%)

Alpha adrenergic Absorbed from upper

Alfuzocin HCL Highly water soluble - 5 75
receptor blocker GIT

Cephalosporin type Degrade in alkaline

Cephalexin - - 1 76
antibiotic pH
Highly soluble in
Ofloxacin Fluoroquinoline - - 9 77
Absorption occurs
Acidic media and
Antidiabetic - - precipitate in upper GIT - -
alkaline media
Low bioavailability (10-
Verapamil Calcium channel
Soluble in water - 20%) due to first pass 4 78
hydrochloride blocker
effect
Rapidly absorbed from
Good solubility in
Domperidone Prokinetic agent - stomach & upper part 7 79
acidic pH but reduced
of GIT
GRDDS: Gastroretentive drug delivery systems
484 VINCHURKAR et al. Gastroretentive Drug Delivery System

from the duodenum, and, when it is radiolabelled, then after its Advantages and applications of gastroretentive delivery
metabolism, the CO2 exhaled in breath can be correlated with systems
the amount of octanoic acid absorbed. The radiolabelled CO2 Gastroretentive dosage forms release the drug in a controlled
was measured by isotope ratio mass spectroscopy.65,66 manner to their specific site of action.74 These systems help
f. Magnetic marker monitoring increase the bioavailability of drugs that get metabolized in
the upper part of the gastrointestinal tract, such as riboflavin
Compared with radiology and scintigraphy, this method is
radiation-less, and thus is non-hazardous.67,68 It involves and levodopa, etc.75,76 For drugs that have a short half-life,
real-time tracking of the dosage form in the gastrointestinal gastroretentive dosage forms help reduce the dosing frequency
tract.69,70 This technique is mainly used for the determination and improve patient compliance by enhancing GRT. Also, they
of the gastrointestinal motility and dissolution behavior of provide a sustained and prolonged release of drugs in the
pharmaceuticals. In this technique, the dosage form is labeled stomach and intestine, which are helpful in local therapy.77-79
as a magnetic dipole by incorporating a trace of ferromagnetic Lastly, Table 3 depicts the gastroretentive technologies adopted
particles and recording the magnetic dipole field by an apparatus by various pharmaceutical companies, and Table 4 represents
responsive to bio-magnetic measurement.71-73 the list of commonly used drugs for various floating systems.

Table 3. Gastroretentive technologies adopted by various pharmaceutical companies

Technology Company Product API References

Lupin, India Xifaxan Rifaximin

Bioadhesive tablets 80
Ofloxacin

Ranbaxy, India Zanocin OD Metformin HCI

Effervescent floating system Riomet OD Ciprofloxacin 81

- Cifran OD

Colloidal gel forming floating system Ranbaxy, India Conviron Ferrous sulphate 82

Sato Pharma, Japan Inon ace tablets Simethicone

Foam-based floating system 83
- - Gabapentin

Polymer-based swelling technology: Depomed, USA Gabapentin GR Ciprofloxacin

84
AcuFormTM - ProQuin XR Metformin HCI

Effervescent and swelling-based floating

Sun Pharma Prazopress XL Prazosin HCI 85
system

Japan Metformin Hcl Metformin HCI

Swelling-based floating system Galenix, France Cafeclor LP Cefaclor 86

- Tramadol LP Tramadol

Roche, UK Madopar Levodopa and benserzide

Floating CR capsule 86
- Valrelease Diazepam

Expandable system (unfloading) Intec Pharma, Israel Accordion PillTM Carbidopa/levodopa 86

Erodible matrix-based system Bayer, USA Cipro XR Ciprofloxacin HCI and betaines 87

Coated multi-layer and swelling system Sun Pharma, India Baclofen GRS Baclofen 88

Gastroretention with osmotic system GlaxoSmithKline, UK Coreg CR Carvedilol 89

Effervescent floating liquid alginate Reckitt Benckiser Alginic acid and sodium
Liquid gaviscon 89
preparation Healthcare,UK bicarbonate

Bilayer-floating capsule Pfizer, UK Cytotec Misoprostol 90

Pierre Fabre Topalkan Aluminium magnesium

Raft-forming system 90
Medicament, France Almagate flatcoat Aluminium magnesium antacid
 VINCHURKAR et al. Gastroretentive Drug Delivery System 485

Table 4. List of commonly used drugs for various floating system82,83,85,87-90

Type of system Drugs used
Rosiglitazone maleate, verapamil, orlistat, aspirin, griseofulvin, acetylsalicylic acid, ibuprofen,
Microspheres tablets/pills
ampicillin, captopril, sotalol, isosorbide dinitrate, terfanadine
Losartan, furosemide, ciprofloxacin, captopril, cinnarazine, sotalol, ampicillin, florouracil, metformin
Tablets
hydrochloride, atenolol, baclofen

Films Cinnarizine, peritanide, quinidine gluconate, albendazole, p-aminobenzoic acid, prednisolone

Ranitidine HCl, diclofenac sodium, cinnarizine, indomethacin, fluorouracil, diltiazem, isosorbide

Granules
dinitrate

Powders Riboflavin, sotalol, theophylline

Capsules Verapamil HCl, chlordizepoxide, diazepam, misoprostol, furosemide, L-DOPA, pepstatin, nicardipine

CONCLUSION 7. Malpure PS, Chavan BR, Maru AD, Bhadhane JS, Thakare EB, Sonawane
PS. Gastroretentive drug delivery systems. World J Pharm Pharm Sci.
GRDDS are unique systems and have become important in
2019;8:506-528.
the last three decades. It offers various advantages, viz., site-
specific, slow, and controlled release of drugs from different 8. Kumar M, Kaushik D. An Overview on various approaches and recent
types of gastroretentive dosage forms, thus improving patient patents on gastroretentive drug delivery systems. Recent Pat Drug Deliv
compliance and reducing the side effects by minimizing dosing Formul. 2018;12:84-92.
frequency. Therefore, it is expected that in the future, various 9. Pund AU, Shendge R, Pote AK. Current approaches on gastroretentive
pharmaceutical companies will come forward to initialize drug delivery system. J Drug Deliv Ther. 2020;10:139-146.
gastroretentive drug delivery technology to create excellent
10. Gunda RK. Formulation development and evaluation of gastroretentive
advantages, prolonging patents, and a better outcome for their
drug delivery system. A review. J Pharm Res. 2017;8:11-20.
marketed formulations.
11. More S, Gavali K, Doke O, Kasgawadek P. Gastroretentive drug delivery
Ethics system. J Drug Deliv Ther. 2018;8:24-35.
Peer-review: Externally peer-reviewed.
12. Tomar A, Upadhyay A, Gupta S, Kumar S. An overview on gastroretentive
Authorship Contributions drug delivery system: current approaches and advancements. Res
Concept: K.V., S.M., P.D., Design: K.V., S.M., J.S., P.D., Pharm Sci. 2019;9:12-16.
Data Collection or Processing: K.V., S.M., P.D., Analysis or 13. Taylor K, Aulton M. Aulton’s Pharmaceutics. The design and manufacture
Interpretation: K.V., S.M., Literature Search: K.V., S.M., Writing: of medicines (4th ed). Churchill Livingstone; London; 2007:397.
K.V., S.M., M.A.K., D.K.M.
14. Gandhi A, Verma S, Imam SS, Vyas M. A review on techniques for grafting
Conflict of Interest: No conflict of interest was declared by the of natural polymers and their applications. Plant Arch. 2019;19:972-978.
authors.
15. Chudiwal V, Shahi S, Chudiwal S, Ahale D. Innovative technologies for
Financial Disclosure: The authors declared that this study gastro-retentive. Asian J Pharm Res 2017;6:22-28.
received no financial support.
16. Devkant S, Anjali S. Gastro retentive drug delivery system. A review.
Asian Pac J Health Sci. 2014;1:80-89.
REFERENCES
17. Clarke GM, Newton JM, Short MB. Comparative gastrointestinal transit
1. Schneider F, Koziolek M, Weitschies W. In vitro and in vivo test methods
of pellet systems of varying density. Int J Pharm. 1995;114;1-11.
for the evaluation of gastroretentive dosage forms. Pharmaceutics.
2019;11:416. 18. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery
system. Expert Opin Drug Deliv. 2006;3:217-233.
2. Boulton DW, Fawcett JP. Enantioselective disposition of albuterol in
humans. Clin Rev Allergy Immunol. 1996;14:115-138. 19. Garg R, Gupta GD. Progress in controlled gastroretentive delivery
3. Chandira RM, Palanisamy P, Jaykar B. Formulation and evaluation of systems. Trop J Pharm Res. 2008;7:1055-1066.
bilayered floating tablets of metformin hydrochloride. Int Res J Pharm. 20. Thapa P, Jeong SH. Effects of formulation and process variables on
2012;3:257-267. gastroretentive floating tablets with a high-dose soluble drug and
4. Menon A, Ritschel WA, Sakr A. Development and evaluation of a monolithic experimental design approach. Pharmaceutics. 2018;10:161.
floating dosage form for furosemide. J Pharm Sci. 1994;83:239-245. 21. Patel A, Modasiya M, Shah D, Patel V. Development and in vivo
5. Levy G, Jusko WJ. Factors affecting the absorption of riboflavin in man. floating behavior of verapamil HCl intragastric floating tablets. AAPS
J Pharm Sci. 1966;55:285-289. PharmSciTech. 2009;10:310-315.
6. Badoni A, Ojha A, Gnanarajan G, Kothiyal P. Review on gastroretentive 22. Nayak AK, Maji R, Das B. Gastroretentive drug delivery systems: a
drug delivery system. J Pharm Innov. 2012;1:32-42. review. Asian J Pharm Clin Res. 2010;3:2-10.
486 VINCHURKAR et al. Gastroretentive Drug Delivery System

23. Nasa P, Mahant S, Sharma D. Floating systems: a novel approach 41. Rocca DJ, Omidian H, Shah K. Progresses in gastroretentive drug
towards gastro retentive drug delivery systems. Int J Pharm Pharm Sci. delivery systems. Business Briefing Pharmatech. 2003;152-156.
2010;2:2-7.
42. Zate SU, Mahale GH, Kapse KP, Anantwar SP. Gastroretentive bioadhesive
24. Zhao Z, Wu C, Zhao Y, Hao Y, Liu Y, Zhao W. Development of an oral drug delivery system: a review. Int J PharmTech Res. 2010;2:1227-1235.
push-pull osmotic pump of fenofibrate-loaded mesoporous silica 43. Madgulkar A, Kadam S, Pokharkar V. Studies on formulation development
nanoparticles. Int J Nanomedicine. 2015;10:1691-1701. Erratum in: Int J of mucoadhesive sustained release itraconazole tablet using response
Nanomedicine. 2022;17:15-16. surface methodology. AAPS PharmSciTech. 2008;9:998-1005.
25. Saisivam S, Ulla MR, Shakeel F. Development of floating matrix tablet 44. Yeole PG, Khan S, Patel VF. Floating drug delivery systems. Need and
of losartan potassium: in vitro and in vivo evaluation. J Drug Deliv Sci development. Indian J Pharm Sci. 2005;67:265-272.
Technol. 2013;23:611-617.
45. Dolas RT, Hosmani A, Bhandari A, Kumar B, Somvanshi S. Novel
26. Moursy NM, Afifi NN, Ghorab DM, El-Saharty Y. Formulation and sustained release gastroretentive drug delivery system: a review. Int J
evaluation of sustained release floating capsules of nicardipine Pharm Res Dev. 2004;2:26-41.
hydrochloride. Pharmazie. 2003;58:38-43.
46. Hardenia SS, Jain A, Patel R, Kaushal A. Floating drug delivery systems.
27. Samal HB, Dey S, Kumar D, Kumar DS, Sreenivas SA, Rahul V. A review. Asian J Pharm Life Sci. 2011;1:284-293.
Formulation, characterization and in-vitro evaluation of floating
microspheres of nateglinide. Int J Pharm Bio Sci. 2011;2:147-157. 47. Desu P, Paasam V, Kotra V. Formulation and in vitro evaluation of
superporous hydrogel based gastroretentive drug delivery system of
28. Pal P, Sharma V, Singh L. A review on floating type gastroretentive drug vildagliptin. J Pharm Res. 2019;23:873-885.
delivery system. Int Res J Pharm. 2012;3:37-43.
48. Joshi P, Patel P, Modi H, Patel MR, Patel KR, Patel NM. A review on
29. Meka L, Kesavan B, Chinnala KM, Vobalaboina V, Yamsani MR. gastro retentive drug delivery system. J Pharm Sci Bio-Sci Res.
Preparation of a matrix type multiple-unit gastro retentive floating drug 2012;2:123-128.
delivery system for captopril based on gas formation technique: in vitro
49. Gröning R, Berntgen M, Georgarakis M. Acyclovir serum concentrations
evaluation. AAPS PharmSciTech. 2008;9:612-619.
following peroral administration of magnetic depot tablets and the
30. Verma R, Kumar A, Purohit S, Bhandari A. Overview of gastro-retentive influence of extracorporal magnets to control gastrointestinal transit.
drug delivery system. J Natura Conscientia. 2011;2:423-436. Eur J Pharm Biopharm. 1998;46:285-291.
31. Atyabi F, Sharma HL, Mohammad HAH, Fell JT. In vivo evaluation of 50. Hilton AK, Deasy PB. In vitro and in vivo evaluation of an oral sustained-
novel gastric retentive formulation based on ion exchange resin. J release floating dosage form of amoxycillin trihydrate. Int J Pharm.
Control Release. 1996;42:105-113. 1992;86:79-88.
32. Ali A, Shahid MA, Hossain MD, Islam MN. Antibacterial bi-layered 51. Sangekar S, Vadino WA, Chaudhary I, Parr A, Beinh R, Digenis G.
polyvinyl alcohol (PVA)-chitosan blend nanofibrous mat loaded with Evaluation of the effect of food and specific gravity of tablets, on gastric
Azadirachta indica (neem) extract. Int J Biol Macromol. 2019;138:13-20. retention time. Int J Pharm. 1987;35:187-191.
33. Nayak AK, Malakar J. Formulation and in vitro evaluation of 52. Patel N, Nagesh C, Chandrashekhar S, Jinal P, Devdatt J. Floating drug
hydrodynamically balanced system for theophylline delivery. J Basic Clin delivery system: an innovative acceptable approach in gastroretentive
Pharm. 2011;2:133-137. drug delivery. Asian J Pharm Res. 2012;2:7-18.
34. Gupta P, Kumar M, Kaushik D. Pantoprazole sodium loaded microballoons 53. Pham AT, Lee PI. Probing the mechanisms of drug release from
for the systemic approach: in vitro and in vivo evaluation. Adv Pharm hydroxypropylmethyl cellulose matrices. Pharm Res. 1994;11:1379-1384.
Bull. 2017;7:461-467.
54. Sharma N, Agarwal D, Gupta MK, Mahaveer PK. A comprehensive review
35. Ghareeb MM, Radhi ZA. Formulation and in vitro evaluation of on floating drug delivery system. Int Res J Pharm. 2011; 2:428-441.
trimetazidine dichloride floating beads. Int J Pharm Pharm Sci.
55. Caldwell LJ, Gardner CR, Cargill RC. Drug delivery device which can be
2014;6:456-440.
retained in the stomach for a controlled period of time. US patent no:
36. Vinchurkar K, Balekar N. Formulation and evaluation of floating 4735804. April 05, 1988.
multilayered coated tablets. J Adv Pharm Technol Res. 2015;212-222.
56. Shivkumar HG, Vishakante GD, Pramodkumar TM. Floating controlled
37. Kim S, Hwang KM, Park YS, Nguyen TT, Park ES. Preparation and drug delivery systems for prolong gastric residence. Indian J Pharm Edu
evaluation of non-effervescent gastroretentive tablets containing Res. 2004;38:172-179.
pregabalin for once-daily administration and dose proportional
57. Singh BN, Kim KH. Floating drug delivery systems: an approach to
pharmacokinetics. Int J Pharm. 2018;550:160-169.
oral controlled drug delivery via gastric retention. J Control Release.
38. Soni RP, Patel AV, Patel RB. Patel NM. Gastroretentive drug delivery 2000;63:235-259.
systems. A review. Int J Pharm World Res. 2011;2:1-24.
58. Burns SJ, Corness D, Hay G, Higginbottom S, Whwlan I, Attwood D,
39. Kuldeep V, Sheetal M, Jitendra S, Masheer K. Formulation and evaluation Barnwell SG. Development and validation of an in vitro dissolution
of once a day dual component gastroretentive drug delivery system. method for a floating dosage form with biphasic release characteristics.
Asian J Sci Technol. 2019;10:10247-10254. Int J Pharm. 1995;121:37-34.
40. Shep S, Dodiya S, Lahoti SR, Mayee R. Swelling system: a novel approach 59. Timmermans J, Moës AJ. Factors controlling the buoyancy and
towards gastroretentive drug delivery system. Indo Global J Pharm Sci. gastric retention capabilities of floating matrix capsules: new data for
2011;1:234-242. reconsidering the controversy. J Pharm Sci. 1994;83:18-24.
 VINCHURKAR et al. Gastroretentive Drug Delivery System 487

60. Hendee WR. In: Textbook of diagnostic imaging. Fundamentals of 76. Sonani NG, Hiremath SP, Dasankoppa FS, Jamakandi VG, Sreenivas
diagnostic imaging: Characteristic of radiographic image. WB Saunders SA. Design and evaluation of gastroretentive mucoadhesive cephalexin
Co, Philadelphia (1th ed). 1994;1:9-10. tablets. Pharm Dev Technol. 2010;15:178-183.
61. Koner P, Saudagar RB, Dharwal SJ. Gastro-retentive drugs: a novel 77. Gangurde HH, Chordiya MA, Tamizharasi S, Senthilkumaran K, Sivakumar
approach towards floating therapy. J Novel Drug Deliv. 2007;1:2211-2215. T. Formulation and evaluation of sustained release bioadhesive tablets
of ofloxacin using 3(2) factorial design. Int J Pharm Investig. 2011;1:148-
62. Biller S, Baumgarten D, Haueisen J. Magnetic marker monitoring:
156.
a novel approach for magnetic marker design. Ifmbe Proceedings.
2010;29:260:263. 78. Gattani SG, Londhe SG, Chalikwar SS, Amrutkar JR. Formulation and
evaluation of gastroretentive drug delivery of verapamil hydrochloride.
63. Bathool A, Gowda DV, Khan MS, Ahmed A, Vasudha SL, Rohitash K.
Eur J Parenter Pharm Sci. 2010;15:125-129.
Development and evaluation of microporous osmotic tablets of diltiazem
hydrochloride. J Adv Pharm Technol Res. 2012;3:124-133. 79. Saritha D, Sathish D, Rao YM. Formulation and evaluation of
gastroretentive floating tablets of domperidone maleate. J Appl Pharm
64. Bhise SB, Aloorkar NH. Formulation and in vitro evaluation of floating
Sci. 2012;2:68-73.
capsule of theophylline. Indian J Pharm Sci. 2008;70:224-227.
80. Jahagirdar HA, Kulkarni R, Kulkarni S. Pharmaceutical composition of
65. Savale S. Formulation and evaluation of metformin HCl microbeads by
rifaximin. U.S. patent 8383151. 2008; June 23.
ionotropic gelation method. Der Pharmacia Lettre. 2016;8:189-196.
81. Mandal UK, Chatterjee B, Senjoti FG. Gastro-retentive drug delivery
66. Arza RA, Gonugunta CS, Veerareddy PR. Formulation and evaluation
systems and their in vivo success: a recent update. Asian J Pharm Sci.
of swellable and floating gastroretentive ciprofloxacin hydrochloride
2016;11:575-584.
tablets. AAPS PharmSciTech. 2009;10:220-226.
82. Gautam CS, Saha L, Sekhri K, Saha PK. Iron deficiency in pregnancy
67. Vinodbhai PK, Gohel M, Suthar S. Sustained release floating
and the rationality of iron supplements prescribed during pregnancy.
microspheres of acyclovir: formulation, optimization, characterization
Medscape J Med. 2008;10:283.
and in vitro evaluation. Int J Drug Dev. 2011;3:242-251.
83. Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future
68. Suthakaran R, Akkala M. Formulation and evaluation of sustained release
perspectives on gastroretentive drug delivery systems. Pharmaceutics.
floating matrix tablet of an antiretroviral drug. JPSBR. 2016;5:82-83.
2019;11:193.
69. Yin L, Qin C, Chen K, Zhu C, Cao H, Zhou J, He W, Zhang Q. Gastro-
84. Pawar VK, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni GT.
floating tablets of cephalexin: preparation and in vitro/in vivo evaluation.
Gastroretentive dosage forms: a review with special emphasis on
Int J Pharm. 2013;452:241-248.
floating drug delivery systems. Drug Deliv. 2011;18:97-110.
70. Munir R, Massud A, Inam S, Umber A. Development and evaluation of
85. Lopes CM, Bettencourt C, Rossi A, Buttini F, Barata P. Overview on
gastroretentive tablet of furesomide. Int J Adv Pharm Res. 2013;4:2362-
gastroretentive drug delivery systems for improving drug bioavailability.
2370.
Int J Pharm. 2016;510:144-158.
71. Wang YP, Gan Y, Zhang XX. Novel gastroretentive sustained-release tablet
86. Prinderre P, Sauzet C, Fuxen C. Advances in gastro retentive drug-
of tacrolimus based on self-microemulsifying mixture: in vitro evaluation
delivery systems. Expert Opin Drug Deliv. 2011;8:1189-1203.
and in vivo bioavailability test. Acta Pharmacol Sin. 2011;32:1294-1302.
87. Achi AA, Gupta MR, Stagner WC. Integrated pharmaceutics: applied
72. Jiménez-Martínez I, Quirino-Barreda T, Villafuerte-Robles L. Sustained
preformulation, Product design, and Regulatory science (1st ed). John
delivery of captopril from floating matrix tablets. Int J Pharm.
Wiley & Sons: New York, 2013:1;1024.
2008;362:37-43.
88. Mishra A, Shahiwala A. In-vitro and in-vivo tools in drug delivery research
73. Sharma M, Kohli S, Dinda A. In-vitro and in-vivo evaluation of repaglinide
for optimum clinical outcomes (1st ed). CRC Press, New York, 2018:1;350.
loaded floating microspheres prepared from different viscosity grades of
HPMC polymer. Saudi Pharm J. 2015;23:675-682. 89. Kotreka UK, Adeyeye MC. Gastroretentive floating drug-delivery systems:
a critical review. Crit Rev Ther Drug Carrier Syst. 2011;28:47-99.
74. Wadher KJ, Kakde RB, Umekar MJ. Formulation and evaluation of a
sustained-release tablets of metformin hydrochloride using hydrophilic 90. Waterman KC. A critical review of gastric retentive controlled drug
synthetic and hydrophobic natural polymers. Indian J Pharm Sci. delivery. Pharm Dev Technol. 2007;12:1-10.
2011;73:208-215.
75. Rudraswamy-Math NR, Gupta VR. Formulation and evaluation of
gastroretentive controlled release tablets of alfuzosin hydrochloride. Pak
J Pharm Sci. 2015;28:2147-2152.