Patole et al Asian Journal of Pharmaceutical Research and Development.

2023; 11(4): 79-94

Available online on 15.08.2023 at [Link]

Asian Journal of Pharmaceutical Research and Development

Open Access to Pharmaceutical and Medical Research
© 2013-22, publisher and licensee AJPRD, This is an Open Access article which permits unrestricted non-
commercial use, provided the original work is properly cited

Open Access Review Article

A Review for Gastro - Retentive Drug Delivery System
Rutuja Patole*, Bharatee Chaware, Vishal Mohite, Vivekkumar Redasani
Yashoda Shikshan Prasarak Mandal's, Yashoda Technical Campus, Faculty of Pharmacy, Satara,

ABSTRACT

Inadequate pharmacokinetic properties may be connected with the widespread use of oral dose forms in disease treatment.
Because of the formulation's rapid transit through the gastrointestinal tract (GIT), it can be challenging to achieve therapeutic
levels of the medicine in specific situations when it is barely soluble; In addition, some medications must work locally due to a
gastric disease, although they only last a short period in the stomach. Numerous studies have been done to identify formulations
that can enhance all of these characteristics while extending stomach residence time. Many orally delivered medications
advantageous for from the extended stomach retention time provided by gastroretentive controlled drug delivery [Link] a
focus on current methods for extending stomach residence duration, the study's objective was to examine, gather, and present the
preceding and contemporary literatures in a shorter format. The current review briefly discusses the need for GRDDS.,
Pharmaceutical importance’s of GRDDS, Physiology of stomach, Stomach functionalities, Approaches of GRDDS, factors
controlling gastric retention, advantages , disadvantages, Method of preparation of Gastro-retentive Multiparticulate system,
Polymeric material in gastroretentive formulations, Evaluation of Gastroretentive dosage form, comparsion between Conventional
and Gastroretentive drug delivery system.
Key Words: Gastroretentive Controlled Drug Delivery Systems, GRDDS, Gastric Retention

A R T I C L E I N F O: Received 21 May 2023; Review Complete 29 June2023; Accepted 05 Aug. 2023; Available online 15 Aug. 2023
Cite this article as:
Patole R, Chaware B, Mohite V, Redasani VK, A Review for Gastro - Retentive Drug Delivery System, Asian Journal of Pharmaceutical
Research and Development. 2023; 11(4):79-94. DOI: [Link]
*Address for Correspondence:
Rutuja Patole, Yashoda Shikshan Prasarak Mandal's, Yashoda Technical Campus , Faculty of Pharmacy, Satara, Maharastra, India.

INTRODUCTION GRDDS is characterised as a system that remains in the

stomach for a sufficient duration of time before releasing

O
ral drug administration has traditionally been the
active moiety in a regulated manner and being metabolised
main method of drug delivery. Over the past two
throughout the body. Numerous GRDDS that extend GRT
decades , a variety of oral delivery systems have
have been developed over the past 20 years. The main goal
been developed to operate as drug reservoirs from which the
of developing GRDDS is to reduce the issues with the
active ingredient can be given over a predefined amount of
current oral sustained release dose form and to create
time at a controlled rate.
patient-beneficial medication delivery[3].
However, there are various physiological issues with this
One novel method in this field is the GRDDS (gastro
technique. Including a variable and unpredictable stomach
retentive drug delivery system). GRDDs are dose forms that
emptying rate, the availability of a drug absorption window
the stomach is able to maintain. GRDDSs can improve the
in the upper small intestine for a variety of drugs, and a brief
regulated administration of drugs with an absorption
gastrointestinal transit time (8–12 hours)[1].To address these
window by continuously releasing the drug for a long time
issues, Researchers have created a drug delivery method that
before it reaches its absorption site[4]. For medications that
lasts an extended period of time in the stomach and
are absorbed from the proximal section of the GIT (gastro
predictable period of time. An effort is being made to create
intestinal tract), are less soluble in alkaline pH, are
a drug delivery system that can deliver a therapeutically
destroyed by alkaline pH, or come into contact at the lower
effective plasma drug concentration for a longer period of
part of the GIT, prolonging the stomach retention of the
time, reducing the frequency of dosing and minimising
drugs may occasionally be beneficial to provide therapeutic
fluctuation in plasma drug concentration at steady state [2].
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benefits. GRDDS are advantageous for such medications by small intestine to treat certain disorders, including[5]-:
enhancing theirBioavailability ,Therapeutics Improved bioavailability ,Improved therapeutic efficacy
efficiency,Possible dosage reduction, Apart from these ,Possible dose reduction, Improves the drug solubility,
benefits, these systems provide other pharmacokinetic which is less soluble in high pH environment for example,
benefits such as the maintenance of consistent therapeutic weakly basic medications like Domperidone, papaverine,
levels above a long period of time and hence a reduction in etc., Reduce drug waste, help in attaining local drug
therapeutic level[5]. distribution to the stomach and proximal small intestine.
Short-half-life drugs and easy absorption from the GIT are For local action in the upper section of the small intestine,
quickly removed from the systemic circulation. To ensure such as the treatment of peptic ulcers, prolonged gastric
appropriate therapeutic activity, these medicines must be retention time in the stomach may be advantageous[7].
dosed often. The development of oral sustained controlled
Oral dose formulations for stomach retention have received
release formulations attempts to overcome this limitation by
increasing interest in recent years due to their therapeutic
gradually releasing the medication into the GIT while
benefit in allowing control over the timing and site of
preserving drugs concentration that is efficient in the
medication release. Many medications classified as once-a-
systemic circulation for a longer duration of time. Using
day delivery have demonstrated on dosage form transit time.
such drug delivery would stay in the stomach after oral
As a result, a system intended for extended stomach
administration and release the medication in a controlled
retention will extend the time available for drug absorption
way, allowing the drug to be continuously supplied to its
in the small intestine[8].
absorption sites in the GIT[6].
The mechanism of solid dose forms' regulated gastric
GRDD devices help with drug absorption over the
retention may include Flotation, Sedimentation, Expansion,
predetermined period of time by staying for a longer period
Modified shape systems or by the simultaneous
of time in the stomach than conventional site-specific drug
administration of pharmacological agents that delay gastric
delivery systems. The following improve as a result: the
emptying
bioavailability, decrease drug waste, enhances the solubility
of medications which are less soluble in environments with Why the need of GRDDS?
high pH levels (such as weakly basic medications like
Certain medications that have been absorbed through the
domperidone and papaverine), it also helps in obtaining drug
deliveryloacally to the stomach and proximal small gastrointestinal tract (typically with short half-lives) are
intestine. quickly eliminated from the circulatory system,
necessitating regular dosing. Innovative technique Gastro-
When creating a site-specific orally given controlled release retentive medication deliveries devices are used to address
dosage form, it is desirable to establish longer gastro this [Link] have high plasma drug concentration, which
residence duration via drug delivery. reduces dose frequency. Another advantage of this approach
is that it eliminates variability in plasma drug concentration
Additionally, prolonged gastric retention of the therapeutic
by delivering the drug in a regulated and consistent manner
moiety can offer a number of advantages for the local and [9]
. The rationale for the use of GRDDS is shown in Figure
prolonged delivery of drugs to the stomach and proximal
No1.[10]

Rationale for the use of GRDDS

Improved Improved Improved Increased Sustained

bioavailability /prolong release
half life stability solubility

Reduced drug Increased Patient Increase

waste and Therapeutic compliance Gastric
Fi
frequent efficiency Retention
dosing g Time

Figure No 1: Rationale for the use of GRDDS

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Importance of GRDDS in the field of Pharmaceutics pushing [Link] separates the stomach from the
duodenum and influences the gastric residence period of
Immediate release oral delivery methods are the most
ingested items. However, the pattern of stomach motility
commonly employed to treat disease because they are
differs between fasting and fed states [13]. The stomach
absorbed only at a specific place. The disadvantages of the
motility pattern is organised into active and dormant
instant release dosage form necessitate the development of
[Link] cycle lasts 90-120 minutes and includes four
Gastro-retentive drug delivery methods. These systems will
phases, as shown in Table No.1 [14]. The stomach motility
aid in the retention of drugs at specific sites for extended
pattern is known as migrating motor complex (MMC) [15].
periods of time. This is accomplished by keeping the dosage
form in the stomach and releasing the drug in controlled
action at particular locations in the stomach, duodenum, and
intestine [11].
Physiology of the Stomach
GRDDS success is dependent on an understanding of
stomach physiology and the accompanying gastric emptying
process. As shown in Figure No. 2, the human stomach is
divided into three anatomical regions: the fundus, the body,
and the antrum (pylorus). The typical volume of a stomach
after a meal is roughly 1.5 l, which varies between 250 and
500 ml during the inter-digestive stages [12]. The section
composed of the fundus and the body serves as a reservoir
for any undigested material, whereas the antrum is the
primary site for mixing action. The antrum, being the lower Figure No 2: Human Stomach
section, acts as a pump for gastric emptying through a
Table No 1: Four phases of migrating motor complex (MMC) [14]
Phase Description Duration[min]
Phase 1 Idle state without any contraction 30 to 60
[basal phase]
Phase 2 Intermittent contraction 20 to 40
[pre-burst phase]
Phase 3 The regular contraction at the maximal 10 to 20
[burst phase] frequency causes the good material to
migrate distally.
Phase 4 Transition period between phase 3 and 0 to 5
phase 1

Stomach Functionalities  Iron preparation for absorption- the acid environment of

the stomach dissolves iron salts, which are required for
 The stomach performs the following functions [16]
iron absorption in the small intestine.
 Temporary storage to allow digestive enzymes, pepsins
 Production and secretion of intrinsic factor needed for
to act
absorption of vitamin B12 in the terminal ileum.
 Pepsins are enzymes that break proteins down into
 Regulation of the passage of gastric contents into the
polypeptides.
duodenum. The pylorus pushes tiny jets of stomach
 Mechanical breakdown- the three smooth muscle layers contents through the pyloric sphincter in the duodenum
let the stomach to serve as a churn, adding gastric juice when the chyme is sufficiently acidified and liquefied.
and liquifying the contents to chime. Parasympathetic The sphincter is normally closed, preventing, backflow
nerve stimulation has enhanced gastric motility and of chime into the stomach.
output.
Approaches for achieving gastric retention
 Water, alcohol, and several lipid-soluble medications are There are several techniques to developing gastro retentive
examples of substances that limit absorption. medication delivery devices. Figure 3 depicts some of the
 Non-specific microbial defence supplied by hydrolytic ways.
acid in gastric juice. Vomiting can occur as a result of
ingesting stomach irritants such as bacteria or
chemicals.

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Approaches for GRDDS

Floating drug delivery system Non floating drug delivery system

Non effervescent drug Effervescent Drug Delivery High density drug

delivery System System delivery system

Hydrodynamically Gas generating drug Bioadhesive /

balanced system mucoadhesive drug
delivery system
delivery system

Micro ballons/ Volatile liquid

hallow containing system Expandable drug
microspheres delivery system

Microporous Magnetic drug

compartment delivery system

Alginate beads
Raft forming system

Figure No 3: Approaches of GRDDS

Non-floating drug delivery systems

1. High density (sinking) drug delivery system 2. Bioadhesive or mucoadhesive drug delivery system
The formulation's density exceeds the density of normal The gastric retention time has extended by adhering the
stomach content. The materials boost density to 1.5-2.4 bioadhesive system for gastric mucous [Link]
gm/cm³. The GI transit time of pellets can be extended from delivery system's adhesion to the stomach wall prolongs
5.8 to 24 hours depending on density. However, the residence time, enhancing bioavailability. Chemicals used
efficiency of this method in humans has not been for mucoadhesion include gliadin, carbopol, lecithin,
demonstrated, and no formulation has been commercialized chitosan, polycarbophil, and carboxymethyl cellulose
[17] [18]
. .Novel adhesive materials produced from bacteria
fimbrae or synthetic counterparts have also been tested for
adhesion to the gut. However, the gastric mucoadhesive
force is insufficient to resist the propulsion force of the
stomach wall. Another disadvantage of this sort of system is
the continual production of mucus and dilution of the gastric
content. Many researchers have experimented with a
synergistic method involving floating and a bioadhesion
system (Figure No. 5: Mucoadhesive drug delivery system).

Figure No 4: High density drug delivery system

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5. Raft forming systems

To achieve sustained drug delivery, these systems are built
with gel-forming polymers and effervescent excipients.
Because they provide a barrier between the oesophagus and
the stomach, these systems are good at achieving a localised
impact. As a result, the device can be used to treat peptic
ulcers and gastroesophageal reflux disease. When these
systems come into touch with stomach fluid, they swell and
create a viscous cohesive gel, resulting in the formation of a
continuous layer known as a raft[19,20]. The antacid raft
forming method, which uses sodium alginate as a gel
forming polymer, sodium bicarbonate, and acid neutralizer
Figure No 5: Bioadhesive or mucoadhesive drug delivery system as gas generating agents, was also recently created. The raft
floats on the gastric fluid due to CO2 production, which
3. Magnetic system
reduces the system's bulk density. The raft can float on the
The dose form incorporates a small magnet in this method, gastric fluid for several hours and release the medicine
and another magnet is placed on the abdomen above the continuously. These rafts are particularly useful for
position of the stomach. The external magnet should be set delivering antacid medications [21]. Because of their low
with precision, which may reduce patient compliance. mechanical strength, these systems are exposed to
MMC[20,22].

Figure No 6: Magnetic system

4. Expandable System Figure No 8: Raft forming systems

These systems have the ability to enlarge and stay in the Floating Drug Delivery System
stomach for prolonged periods of time. These are frequently Mechanism of floating drug delivery system
presented in the form of capsules that include a folded and
compressed dosing form. The dosage form expands and the Floating drug delivery systems (FDDS) float in the stomach
capsule shell breaks down in the stomach environment, for a long time without slowing down the gastric emptying
making it unable to pass through. Drug distribution that is rate since they have a lower bulk density than gastric fluids.
maintained and under control can be accomplished by As depicted in Figure No. 9(a), the medication is gradually
employing the right polymer. released from the body at the required pace while the system
is floating on the contents of the stomach. To maintain the
dose form consistently buoyant on the surface of the meal,
however, a minimal amount of floating force (F) is also
necessary in addition to the minimal stomach content
needed to achieve the buoyancy retention principle. The
literature has established a specific method for calculating
resultant weight to evaluate the dynamics of the floating
force. The equipment works by continually measuring the
force equivalent to F (as a function of time) required to keep
the submerged object submerged. If F is on the positive side,
the object floats better, as seen in Figure No. 9. This
equipment helps to optimise FDDS in terms of the stability
and lifespan of the created floating forces, avoiding the
negative effects of unanticipated intragastric buoyancy
capacity changes[23].
Figure No 7: Expandable System F = F buoyancy – F gravity = (Df – Ds) gv

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Where, F= total vertical force, Df = fluid density,Ds= object density, v = volume, g = acceleration due to gravity

Figure No 9: Mechanism of floating drug delivery system

1. Effervescent System juices. Salts and citric/tartaric acid emit CO2, which
becomes trapped in the system's jellified hydrocolloid layer,
These systems was further classified into
lowering its specific gravity and causing it to float over the
a. Gas generating System chime[24]. The system is made up of a sustain release pill as
the seed, which is surrounded by a double layer. The inner
The main process at work in this system is the formation of
layer is a bubbly layer comprising sodium bicarbonate and
CO2 gas as a result of the reaction of sodium bicarbonate,
tartaric acid. The outer layer is a PVA shellac-containing
citric acid, and tartaric acid. The gas created reduces the swellable membrane layer. (Figure No.10: effervescent drug
density of the system, causing it to float on the stomach delivery method.)

Figure No 10: Gas generating System

b. Volatile liquid containing system volatile system. These systems are further classified as
follows:
These have an inflatable chamber that holds a liquid, such as
ether or cyclopentane, which gasifies at body temperature  Intra gastric floating gastrointestinal drug delivery
and causes the chamber in the stomach to inflate. These system-
systems osmotically regulate a floating system with a
specified hollow unit. The system has two chambers, the This method includes a flotation chamber filled with
first containing the medicine and the second containing the vacuum or an inert, harmless gas, as well as a micro porosity
compartment containing a medication reservoir.

Figure No 11: Intra gastric floating gastrointestinal drug delivery system

 Inflatable gastrointestinal drug delivery system- contains bioerodible polymer filament (e.g., a copolymer of
polyvinyl alcohol and polyethylene) that gradually dissolves
At body temperature, an inflatable chamber holding liquid in gastric fluid, causing the inflated chamber to release gas
ether gasifiers to inflate the stomach. The inflatable chamber and collapse.

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Figure No 12: Inflatable gastrointestinal drug delivery system

 Intra-gastric osmotically controlled drug delivery superporous hydrogels are a good example. The dose form
system- expands to several times its original volume when it comes
in contact with gastric fluid. Due to the dose form's bigger
It is made up of an inflatable floating capsule and an size, the gastric contraction slips over the system's surface,
osmotic pressure regulated medication delivery [Link] pushing the dosage form back into the stomach after the
inflatable capsule disintegrates in the stomach, releasing the gastric contraction has pushed it to the pylorus.
osmotically regulated drug delivery system, which is made
up of two parts: a drug reservoir compartment and an
osmotically active compartment. Working on this method,

Figure No 13: Intra-gastric osmotically controlled drug delivery system

[25]
2. Non-effervescent system emptying rate. The medicine is gently released from the
system while the system is floating on the gastric contents at
a. Hydrodynamically balanced system
the desired rate. Following the system's slow release at the
It is a medication formulation containing gel-forming desired rate. The residual system is emptied from the
hydrocolloids designed to remain buoyant in the stomach stomach once the medication is released. As a result, GRT
[Link] drug delivery systems have a lower bulk increases and variations in plasma medication
density than gastric fluids, they can float in the stomach for concentrations are better controlled.
an extended period of time without altering the gastric

Figure No 14: Hydrodynamically balanced system

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b. Micro balloons are dissolved in an ethanol/dichloromethane solution, which

is then put into an agitated solution of Poly Vinyl Alcohol
Micro balloons (Hollow microspheres) are, strictly
(PVA) that is thermally regulated at 40℃ .After the
speaking, empty spherical particles with no core. These
emulsion has solidified into a stable state, the organic
microspheres are often free-flowing powders made of
solvent is removed from the mixture by raising the
proteins or synthetic polymers, with a size of fewer than 200
temperature under pressure or by constant stirring.
micrometres. To construct a hollow inner core in micro
Dichloromethane evaporates in the droplet of dispersed
balloons loaded with medicine in their outer polymer shell,
polymer to form the gas phase inside the hollow interior
innovative technologies such as solvent evaporation are
cavity of the polymer microsphere.
used. The medication and an enteric acrylic polymer mixture

Figure No 15: Micro balloons

c. Microporous compartment
The drug reservoir is contained inside a microporous compartment with pores along its top and bottom walls in this
arrangement. The delivery system floats over the gastric fluid, which enters through the aperture, dissolves the medicine, and
transports the dissolved drug to the stomach and proximal part of the small intestine for absorption.

Figure No 16: Microporous compartment

d. Alginate beads
Calcium alginates that have been freeze dried have been used to create multi unit floating dosage forms [26]. Spherical beads
of about 2.5 mm diameter can be made by dropping sodium alginate solution into an aqueous solution containing calcium
chloride. These beads are separated and dried by air. As a result, an aporous system forms, which remains buoyant in the
stomach.

Figure No 17: Alginate beads

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Factors controlling GRDDS [27,28,29]

Factors controlling GRDDS are shown in Figure 18 and some of the factors are enumerated below

Volume of GI Fluid Concomitant Intake of Drug Effect of Buoyancy

Factors Controlling GRDDS

Formulation factors : Food Intake and its nature Patient related factors
Dosage Form Related
Factors

Density of Fed or Unfed Gender

dosage form State
Age
Size of dosage Nature of meal
form
Disease state
Caloric Content
Shape of dosage
Emotional state
form Frequency of
of subject
food
Viscosity grade
of polymer Posture

Single or
multiple unit Upright Position Supine Position
Formulation

Figure No 18: Factors Controlling GRDDS

1. Density: Low density dosage forms might float to the 5. Fed or Unfed State: Due to an increase in stomach
top of the stomach's contents whereas high density motility, gastric retention time decreases during fasting
dosage forms sink to the bottom. Less than 1.0 gm/cm³ conditions.
of suitable density is required for floating property.
6. Nature of Meal: Variations in stomach motility cause a
2. Size: Size should be more than 7.5 mm in diameter. high concentration of fatty acids and other indigestible
polymers to prolong the gastric retention time.
3. Shape: Either round or spherical shaped dosage form
exhibit better property related to other shapes. 7. Frequency of Feed: Low frequency of migrating
myoelectric complex (MMC) contributes to GRT upto
4. Single or multiple unit formulation: Multiple units are
400 times which inturn depends on the frequency of food
desirable due to foretell release profile.
intake.

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8. Caloric Content: A diet strong in protein and fat can 6. Minimization of fluctuations in drug concentration
raise GRT by 4 to 10 hours.
It enables the evoked pharmacological impact of medicines
9. Gender: GRT is higher in men than in women. that activate different types of receptors at varying doses to
be more selective.
10. Age: GRT is more prevalent in senior individuals and
less prevalent in newborns and kids. Ages greater than 7. Reduced counter-activity of the body
70 (>70) show longer GRT.
In many circumstances, the pharmaceutical response that
11. Posture: Between the patient's supine and upright interferes with the body's natural physiologic processes
ambulatory phases, GRT can change causes a rebound activity that reduces drug activity. Slow
drug delivery into the body has been proven to reduce
12. Disease State: The GRT changes in people with gastric
counter-activity, resulting in improved drug efficiency.
diseases such diabetes, chron's disease, hypothyroidism,
hyperthyroidism, duodenal ulcers, etc. 8. Extended time over critical (effective) concentration
13. Concomitant Intake of Drug: GRT is impacted when For certain medications having non-concentration dependent
some medications are taken with Gastric motility pharmacodynamics, such as etalactam antibiotics, the
enhancers or depressants. clinical response is connected with the period of time over a
key therapeutic concentration rather than the peak
Advantages of Gastro-retentive Drug Delivery Systems
concentration. The sustained mode of administration allows
1. Enhanced bioavailability for the prolonging of time above a critical concentration,
which increases pharmacological effects and therapeutic
The bioavailability of riboflavin CR-GRDF is much higher
results.
than that of non-GRDF CR polymeric formulations. There
are various processes associated to medication absorption 9. Minimized adverse activity at the colon
and transit in the gastrointestinal system that function in
The drug's retention in the GRDF in the stomach reduces the
concert to determine the magnitude of drug absorption[30].
amount of drug that reaches the colon. As a result, unwanted
2. Enhanced first-pass biotransformation pharmacological actions in the colon may be avoided. The
reason for GRDF formulation of beta-lactam antibiotics,
The pre-systemic metabolism of the tested compound may
which are only absorbed from the small intestine and whose
be significantly increased when the drug is presented to the
presence in the colon results in the development of
metabolic enzymes (cytochrome P450, specifically
microbial resistance, is provided by this pharmacodynamic
CYP3A4) in a sustained way as opposed to by a bolus input, feature.
similar to the increased efficacy of active transporters with
capacity limited activity[31]. 10. Site specific drug delivery
3. Sustained drug delivery/reduced frequency of dosing A floating dose form is a viable option, particularly for
medicines with limited absorption sites in the upper small
Sustained and slow input from CR-GRDF may result in flip-
intestine[33]. Controlled, gradual drug administration to the
flop pharmacokinetics and permit lower dosing frequency
stomach gives adequate local therapeutic levels while
for medicines with relatively short biological halflife. This limiting systemic exposure to the drug. This lowers the
trait is linked to increased patient compliance, which adverse effects of the medication in the bloodstream.
enhances therapy.
Furthermore, the increased gastrointestinal availability
4. Targeted therapy for local ailments in the upper GIT provided by a site-directed administration device may
minimize dose frequency.
Prolonged and sustained medication administration from
GRDF to the stomach may be useful for local therapy in the Disadvantages of Gastro-retentive Drug Delivery System
[34]
stomach and small intestine. Therapeutic medication
concentrations can be achieved locally while systemic Unsuitable for drugs with solubility or stability issues in the
concentrations are modest as a result of drug absorption and
GI tract.
distribution.
Drugs that irritate the stomach mucosa are likewise not
5. Reduced fluctuations of drug concentration appropriate.
In comparison to instant release dosage forms, continuous The high turnover rate of gastric mucus poses significant
drug input after CRGRDF treatment results in blood drug challenges for bio adhesive systems, and irritants to the
concentrations within a tighter range. As a result,
gastric mucosa are likewise unsuitable.
oscillations in pharmacological effects are reduced, and
concentration-dependent adverse effects associated with Drugs that absorb selectively in the colon, such as
peak concentrations can be avoided. This property is corticosteroids.
especially important for medications with a limited
To float and perform efficiently, floating medicine delivery
therapeutic index[32].
systems require a high fluid level in the stomach.
Unsuitable for medications that require an unstable, acidic
environment, Erythromycin, for example.

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Methods of Preparation of Gastro-Retentive an external aqueous poly (vinyl alcohol) solution and stirred
Multiparticulate System to allow [Link] were
sieved, rinsed with water, and dried in a desiccator because
1. Solvent Evaporation Method
they were irregular in shape and highly porous. Importantly,
To construct the hollow inner core of a floating the drug encapsulation efficiency was high and nearly
multiparticulate dosage form, solvent diffusion and independent of the system's theoretical loading. Good in-
evaporation processes can be [Link] drug is either vitro floating behaviour was seen in all cases. Surprisingly,
dissolved or disseminated in the polymer solution, which the examined compositions produced a wide range of
has been dissolved in an organic solvent. The medicine release patterns. Further research focused on the creation of
solution is then used to create oil in water emulsion by being a better production procedure for this sort of low density,
emulsified into an aqueous phase with the proper ingredient foam-based, floating microparticle, as well as the
(surfactants/polymer). After the formation of a stable demonstration of the system's in vitro performance [41]. The
emulsion, the organic solvent is evaporated either by raising proposed innovative preparation technique has several
the temperature under pressure or by constant advantages, including quick processing periods, no exposure
stirring[35,36].The elimination of the solvent causes of the materials to high temperatures, the opportunity to
polymer precipitation at the oil/water interface of droplets, avoid harmful organic solvents, and high encapsulation
producing cavities and hollowing them out to give them efficiencies. Floating microparticles were made by soaking
floating qualities. For the development of such systems, microporous foam particles in an organic solution of the
polymers such as cellulose acetate, chitosan, Eudragit, drug and polymer, followed by drying[42].In most cases,
Acrycoat, Methocil, polyacrylates, polyvinyl acetate, good in-vitro floating behaviour was observed, and a wide
carbopol, agar, polyethylene oxide, and polycarbonates have range of drug release patterns could be created by altering
been investigated[37]. the drug loading and type of second polymer [43].
2. Ionotropic Gelation Method 5. Melt Granulation Technique
Ionotropic gelation is supported by poly electrolytes' Melt granulation is a method that produces granules by
capacity to cross link in the presence of opposing ions to adding either a molten binder or a solid binder that melts
form beads. The ionotropic gelation technique has become throughout the operation. This is also known as melt
popular with the use of alginates, gellan gum, chitosan, and agglomeration or thermoplastic granulation[44,45,46,47].
carboxymethyl cellulose for medication and cell
Principle of Melt granulation:
encapsulation[38]. Despite having the property of coating on
the drug core and acting as release rate retardants, natural The process of granulation consists of a combination of
poly electrolytes contain some anions in their chemical three phases:
structure. By interacting with polyvalent cations, these
a. Wetting and nucleation,
anions create meshwork structures and promote gelation by
attaching primarily to anion blocks. Dropping a drug-loaded Wetting and Nucleation process
polymeric solution into an aqueous solution comprising
polyvalent cations yields the hydrogel beads[39]. During the nucleation process, the binder comes into contact
with the powder bed, resulting in the production of tiny
3. Emulsion Solvent Diffusion Method agglomerates. mSchafer and Mathiesen propose two
nucleation mechanisms.
The affinity between the drug and the organic solvent is
stronger in the emulsion solvent diffusion method than Immersion
between the organic solvent and the aqueous solvent.
Despite the fact that the organic solvent is miscible, the When the size of the molten binder droplets is larger than
medication is dissolved in it and the solution is dispersed in that of the small solid particles, nucleation by immersion
takes place.
the aqueous solvent, resulting in emulsion droplets. The
organic solvent gradually diffuses out of the emulsion Fine solid particles are deposited onto the surfaces of molten
droplets into the surrounding aqueous phase, while the binder droplets as immersion progresses.
aqueous phase diffuses into the droplets that crystallise the
medication. Distribution

4. Novel Method for Foam Powder A molten binding liquid is applied to the surfaces of tiny
solid particles using the distribution method.
A novel multi-particulate gastroretentive drug delivery
method based on low-density foam powder has also been The collision of the wetted particles produces the nuclei.
presented and tested in vitro[40]. Floating microparticles Small binder droplet size, low binder viscosity, and large
were created using an oil-in-water solvent extraction / shearing pressures are often favourable circumstances for
evaporation process using polypropylene foam powder, nucleation via the distribution approach.
verapamil hydrochloride (as the model drug) and Eudragit
RS, ethyl cellulose, or poly (methyl methacrylate). b. Coalescence step
Methylene chloride was used to dissolve the medication and In order to increase the success of fusion nuclei, it involves
the polymer that controlled the release rate. Within this nuclei with leftover surface liquid.
organic phase, polypropylene foam powder was then
[Link] resultant suspension was then emulsified in

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Patole et al Asian Journal of Pharmaceutical Research and Development. 2023; 11(4): 79-94

The surface liquid gives the nuclei plasticity and is polycarbophil into HPC films significantly improved
necessary for the nuclei's surface to deform for coalescence bioadhesion when compared to the film containing HPC and
as well as to facilitate granulation rounding. PEG 3350.
c. Attrition and breakage Hydroxyethyl cellulose (HEC) is used as a gelling and
thickening ingredient in the creation of biostructures for the
Attrition and breakage are granulation fragmentation
delivery of hydrophobic medicines. Enalaprilmucoadhesive
phenomena that are solidified by tray cooling to ambient
films, for example, were created using combinations of HEC
temperature without the need for tumbling drying.
and sodium carboxymethylcellulose and shown beneficial
As a result, breaking is known to play a more important role swelling characteristics as well as regulated drug release [51].
in influencing the final parameters of the melt granulation Hydroxyethyl cellulose (HEC), like HPC, has been added in
during the granulation phase. multicomponent polymeric matrices to give the required
gastro-retentive characteristics. Pentoxifylline effervescent
Requirements of Melt granulation floating tablets have been produced successfully employing
In general, a meltable binder concentration of 10-30% w/w sodium bicarbonate as a gas-forming agent and a polymeric
in comparison to fine solid particles is utilised. matrix of sodium alginate and HEC, for example.
A meltable binder suited for granulation has a melting point 3. Carboxymethyl cellulose (CMC)
that is typically between 50-100°C Carboxymethyl cellulose (CMC) is a semisynthetic, non-
Hydrophilic meltable binders are employed in the toxic, water-soluble cellulose derivative that contains
preparation of immediate-release dosage forms, whereas carboxymethyl groups (-CH2-COOH) connected by an ether
hydrophobic meltable binders are preferred in the bond to some of the hydroxyl groups of the cellulose
preparation of prolonged-release formulations. backbone's glucopyranose repeating units. Because the
carboxylate groups in NaCMC are anionic, interactions with
Fine solid particle melting points should be at least 20°C nonionic hydrocolloids such as HPMC and HEC may
higher than the maximum processing temperature. increase their gel-viscosity properties [51].
6. Meltable Binders 4. Natural Gums
Its physical and chemical stability. It must be solid at room Natural polymers, in addition to manufactured cellulose
temperature and melt between 40 and 80°C. ethers, have been employed as hydrocolloids to successfully
Its hydrophilic-lipophilic balance (HLB) ensures proper control drug release from swellablesystems[52] . Natural
active ingredient release. polymers contain beneficial properties such as
biocompatibility and safety, and so have valuable
There are two type of Meltable binder: pharmaceutical and biological applications. Natural gums—
a) Hydrophilic meltable binders gellan gum, guar gum, carrageenans, and xanthan gum—
along with other polysaccharides like alginates and chitosan
b) Hydrophobic meltable binder and natural polymers like pectin and gelatin —are natural
Polymeric Materials InGastroretentive Formulations hydrocolloids or gel-forming agents that can swell in contact
with gastric fluid, maintain relative shape integrity, and have
1. Hydroxypropylmethyl Cellulose (HPMC) a bulk density less than the gastric content[53,49].
Hydroxypropyl methylcellulose (HPMC) is the most widely 5. Guar gum
utilised hydrophilic carrier material in the manufacture of
oral controlled drug delivery systems [48]. One or more of the Guar gum is a polysaccharide derived from the seeds of
three hydroxyl groups from the cellulose glucopyranose Cymopsistetragonolobus (Leguminosae family). Due to the
units have been changed in HPMC, commonly known as dual composition of guar gum: an approximately 85 percent
hypromellose, a cellulose ether, creating ether bonds. Thus, water-soluble fraction known as Guaran and an insoluble
it is a semisynthetic polymer derived from highly purified component, it swells quickly in the presence of water with a
natural pulp and etherified with a mixture of methyl chloride translucent suspension. The addition of borate ions to
and propylene oxide to generate a water-soluble, non-ionic hydrated guar gum forms cohesive structural gels due to the
cellulose ether[49] . The most often used marketed HPMC is mannose units[49] . When employed in solid dosage forms,
sold under the brand names Methocel® and Pharmacoat®. guar gum enhances viscosity and works as a disintegrant and
binder in the pharmaceutical industry[53].
2. Hydroxypropyl cellulose (HPC) and hydroxyethyl
cellulose (HEC) 6. Carrageenans
HPC has been used as the principal matrixforming polymer Carrageenans are anionic polysaccharides with a high
in formulations made utilising hot-melt extrusion and 3D molecular weight generated from Rhodophyceae red
printing technologies due to its low Tg, indicating that the seaweeds. Because of their high durability, good
formulations may be treated at a low temperature. HPC has compatibility, and persistent viscoelasticity of the tablet
demonstrated the potential to create bioadhesive films[50] . throughout granulation and compression, they proved useful
The effect of different additives on the bioadhesive as tablet excipient agents. Carrageenans are thus suitable
properties of HPC-based films was investigated, and it was excipients for long-acting formulations. Notably, the
discovered that incorporating Carbomer 971P and a carrageenans' actual density measurements were found to be

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Patole et al Asian Journal of Pharmaceutical Research and Development. 2023; 11(4): 79-94

much greater than those of the cellulose ethers (MC, HPMC, after it is placed in the medium. These parameters can be
NaCMC, and HPC)[53]. measured as a part of the dissolution test.
7. Gellan Gum 2. Specific Gravity / Density- The displacement method,
using Benzene as the displacement medium, can be used
When Ca2+ ions are present as a crosslinking agent, gellan
to calculate density.
gum can be used for in-situ gel formation. Gellan gum can
be utilised as a crosslinking agent in in-situ gels when 3. Resultant Weight-The two fundamental factors that
combined with Ca2+ ions. define buoyancy are bulk density and floating time.
However, a single measurement of density is insufficient
8. Xanthan Gum
to fully represent buoyancy since density varies over
Because it is non-toxic and non-irritant, xanthan gum is used time as a function of changes in the resulting weight. For
in food, cosmetics, and topical and oral medicinal example, a matrix tablet containing bicarbonate and a
formulations. Its presence influences the zero-order kinetics matrixing polymer initially floats due to gas production
of drug release from formulations [54]. and entrapment, but after some time, a certain drug is
released and at the same time, some of the matrixing
9. Crosslinkedpolyacrylates: Carbomers, Carbopol® polymer's outer layer may erode away, changing the
and Polycarbophyl (PCP) dosage form's final weight.
Carbomers are high-molecular-weight synthetic polyacrylic
4. Swelling systems
acids that are cross-linked with polyalcohol allyl ethers such
as pentaerythritolpolyallylether and polyallyl sucrose. Swelling Index-The dosage form is taken from the SGF at
Carbopol® polymer grades differ in terms of physical regular intervals after being immersed in a swelling solution
structure and chemical composition, crosslink density, at 37°C, and dimensional changes are measured as an
polymerization solvent, crosslinking type, network electrical increase in tablet thickness or diameter with time.
charge, and physical appearance, and thus in terms of
Water Uptake- It is an indirect measurement of swelling
performance. Carbomers require polymer ratios of 3 to 30%
property of swellable matrix. Here dosage form is removed
when used as controlled release polymers in matrix tablets.
out at regular interval and weight changes are determined
Carbopol and polycarbophil hydrogels are generally
with respect to time. Water uptake = WU = (Wt – Wo) *
extremely permeable to a wide range of pharmacological
100 / Wo
substances and can be designed to "swell," releasing
entrapped molecules via their network-like Structure[55,56]. Where, Wt = weight of dosage form at time t.
The drug release can be fine-tuned by altering the polymer
Wo = initial weight of dosage form[60].
concentration.
5. Particle Size and Shape
10. Poly(ethylene oxide)(PEO)
In comparison to light microscopy (LM), scanning electron
High molecular weight PEO has been effectively used in
microscopy (SEM) delivers better resolution. The most
controlled release dosage forms because the rate of swelling
common methods for visualising microparticles are light
and erosion of the polymer allows for sustained release of
microscopy (LM) and scanning electron microscopy (SEM).
APIs. High molecular weight PEO is viscoelastic in its
Both are capable of determining the shape and exterior
swollen state because it can form dense polymeric networks
structure of a multiparticulate. In the case of double-walled
in aqueous environments [57]. PEO is thus relevant as an
microspheres, LM allows for control over coating settings.
additive for improving the mechanical properties of highly
Before and after coating, the Multiparticulate formations can
swellable and mechanically strong matrix tablets.
be seen and measured microscopically. SEM can investigate
11. Kollidon® SR multiparticular surfaces, and after particles are cross
sectioned, it can also investigate double walled systems.
Kollidon® SR is a poly(vinyl acetate) (PVAc) and povidone
Conflocal fluorescence microscopy is used to characterise
(poly(N-vinyl pyrrolidone) (PVP) mixture used largely as a
the structure of multiple walled microspheres. Other than
matrix retarding agent. It is ideal for direct compression or
instrumental approaches, laser light scattering and multi size
hot melt extrusion of pH-independent sustained-release
coulter counter can be employed to characterise the size,
matrix tablets. PVAc is a polymeric material that, even
shape, and morphology of the Multiparticulate[61].
when subjected to low compression pressures, forms a
cohesive matrix. When the tablets are dissolved in stomach 6. Entrapment Efficiency -
or intestinal fluid, the water-soluble PVP is leached out,
By allowing washed multiparticulate to lyse, the
resulting in holes through which the active ingredient slowly
multiparticulate's capture effectiveness or the percent
diffuses. Kollidon® SR is drug compound inert, and its
entrapment can be calculated. The active ingredients of the
sustained-release properties are unaffected by ions or salts
lysate are then determined in accordance with the
because it lacks ionic groups [58,59].
requirements of the monograph. Equation is used to
Evaluation of gastro-retentive dosage form calculate the percent encapsulation efficiency.
1. Buoyancy Lag Time- % Entrapment = Actual content/Theoretical content x 100
It is determined in order to assess the time taken by the
dosage form to float on the top of the dissolution medium,

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Patole et al Asian Journal of Pharmaceutical Research and Development. 2023; 11(4): 79-94

7. Floating Behavior- a. Radiology X-ray is widely used for examination of

internal body systems. Barium Sulphate is widely used
In 100 ml of the simulated gastric fluid (SGF, pH 2.0), the
Radio Opaque Marker.
appropriate amount of the floating microparticulate is added,
and the mixture is agitated using a magnetic stirrer. b. Scintigraphy emitting substances are incorporated into
Filtration is used to remove the layer of buoyant dosage forms, much like with X-rays, and then images
microparticulate after pipetting. Filtration separates the are captured using scintigraphy. Widely used emitting
particles in the sinking particulate layer. Both kinds of material is 99Tc[64]
particles are dried in a desiccator until they have a constant
c. Gastroscopy peroral endoscopy using fibre optics or
weight. Both microsphere fractions are weighed, and the
video technologies is known as gastroscopy. The use of
weight ratio of the floating particles to the total of the
gastroscopy allows for a visual examination of the
floating and sinking particles is used to calculate buoyancy.
effects of stomach extension[65].
Buoyancy (%) = Wf / Wf + Ws.
d. Magnetic Marker Monitoring This method uses an
Where, Wf and Ws are the weights of the floating and iron powder-filled dosage form that is magnetically
settled microparticles [62]. marked so that images can be captured by highly
sensitive biomagnetic measurement equipment.
8. In Vitro Release Studies
Advantage of this method is that it is radiation less and
In a dissolution apparatus, the rate of release of floating so not hazardous.
microparticulate is determined. A weighted amount of
e. Ultrasonography used sometimes, not used generally
floating microspheres equal to the medicine dose is taken
because it is not traceable at intestine.
and placed in the dissolving rate apparatus basket. During
the drug release research, the dissolving fluid is kept at 37 ± f. 13C Octanoic Acid Breath Test 13C Octanoic acid is
0.5°C with a rotation speed that produces sink conditions [63]. incorporated into GRDDs. In stomach due to chemical
reaction, octanoic acid liberates CO2 gas which comes
9. Drug – Excipient interaction study
out in breath. The 13C isotope takes the place of the
FT-IR spectroscopy, differential scanning calorimetry, and significant Carbon atom that will be present in CO2.
high performance liquid chromatography can be used to Therefore, the length of time that 13CO2 gas remains in
investigate it. the breath can be regarded as the dose form's stomach
retention period. No reaction takes place, and no CO2 is
10. In vivo Evaluation Test released while the dose form travels to the colon.
Consequently, this approach is less expensive than
others.
Comparsion between Conventional and Gastroretentive Drug Delivery System [34]

Table No 2: Comparsion between Conventional and Gastro-retentive Drug Delivery System

Sr. no Parameter CDDS GRDDS

1 Toxicity High risk of toxicity Low risk of toxicity

2 Patient Compliance Less Improves patient compliance

3 Drug with narrow absorption window in Not suitable Suitable
small intestine

4 Drug acting locally in the stomach Not much advantageous Very much advantageous
5 Drugs having rapid absorption through GIT Not much advantageous Very much advantages

6 Drugs which degrades into colon Not much advantageous Very much advantages

7 Drugs which are poorly soluble at an alkaline Not much advantageous Very much advantages
pH
8 Dose dumping High risk of dose dumping No risk of dose dumping
9 Drug Beneficial for drugs- Not beneficial for drug –
That have rapid GI absorption That have low GI absorption
Degrade in colon Degrade in colon
That show local action in the That show local action in the
stomach stomach

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Patole et al Asian Journal of Pharmaceutical Research and Development. 2023; 11(4): 79-94

17. Clarke GM, Newton JM and Short MD. Gastrointestinal transit of

pellets of differing size and [Link] journal
pharmaceutics. 1993;100(13):81-92.

CONCLUSION 18. Moes AJ. Gastric retention system for oral drug [Link]
[Link]. 2003;157-159.
The oral drug administration route is the most common 19. Prajapati VD, Jani GK, Khutliwala TA, Zala BS. Raft forming
since it is straightforward to utilise. The stomach and systeman upcoming approach of gastroretentive drug delivery system. J
intestines are where oral medications are primarily Control Release 2013;168:151-65.
absorbed. Gastro-Retentive Drug Delivery System 20. Abouelatta SM, Aboelwafa AA, El-Gazayerly ON. Gastroretentive raft
(GRDDS), a drug delivery system that can prolong the liquid delivery system as a new approach to release extension for
contact period with the stomach, is therefore necessary. A carrier-mediated drug. Drug Deliv 2018;25:1161-74.
long-term drug delivery system that can retain drugs in the 21. Hampson FC, Jolliffe IG, Bakhtyari A, Taylor G, Sykes J, Johnstone
stomach for extended periods of time is the GRDDS. LM, et al. Alginate-antacid combinations: Raft formation and gastric
GRDDS has the power to boost bioavailability, improve the retention studies. Drug DevInd Pharm 2010;36:614-23.
solubility of drugs that aren't very soluble in alkaline 22. Abou Youssef NA, Kassem AA, El-Massik MA, Boraie
solutions, regulate therapeutic levels to prevent fluctuations, [Link] of gastroretentive metronidazole floating raft system
and lengthen the half-life to reduce the need for repeated for targeting Helicobacter [Link] J Pharm 2015;486:297-305.
dosing. 23. Garg S, Sharma S. Gastroretentive Drug Delivery System. Business
Briefing: Pharmatech.2003; 160-166.
REFERENCE
24. Misra SK. Gastrointestinal targetting drug delivery system: A Review.
1. Rouge N, Buri P, Doelker E.; Drug Absorption Sites in the Journal of Pharmacy Research. 2011;4(8):2751- 2754.
Gastrointestinal Tract and Dosage Forms for Site Specific Delivery;
IntJPharma. 1996; 136:117-139. 25. Rao BP, Kottan NA, Snehith VH and Ramesh C. Development of
gastroretentive drug delivery system of Cephalexin by using factorial
2. Streubel A, Siepmann J, Bodmeier R; Gastroretentive Drug Delivery design. ARE Pharmaceutical. 2009;50: 8.
System; Expert Opin Drug Delivery; 2006; 3 (2): 217-233.
26. Sheth PR and Tossounian J. The hydrodyanamically balanced system.
3. Kothari Abhaykumar H, Jaimini Manish, Gastroretentive drug delivery A novel drug delivery system for oral [Link] delivery Indian
system and its approaches: a review, International journal of Pharmaceutics. 2010;3(1):819-833.
pharmaceutical research and development, 2013, 4(12), 7-18.
27. Sharma N, Agarwal D, Gupta M and Khinchi M: A comprehensive
4. Singh BN and Kim. Floating drug delivery systems: an approach to review on floating drug delivery system. International Journal of
controlled drug delivery via gastric retention. J. Control. Release.2000; Research in Pharmaceutical and Biomedical sciences 2011; 2:428-441.
63: 235-239.
28. Vasa S and Banji D: Approaches for gastrotentive drug delivery
5. Ali J, Arora S, Khar RK. Floating drug delivery System: A Review. systems. International Journal of Applied Biology and Pharmaceutical
AAPS Pharm Sci Tech. 2005; 06(03): E372-E390. Technology 2010; 1:589-601
6. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery 29. Bhardwaj L, Sharma PK and Malviya R: A short review on gastro
system. Expert Opin Drug Deliv 2006; 3(2): 217-233. retentive formulations for stomach specific drug delivery: special
emphasis on floating in-situ gel systems. African Journal of Basic and
7. Garg R, Gupta GD. Progress in controlled gastroretentive delivery Applied Sciences 2011; 3:300-312.
[Link]. J Pharm Res 2008; 7(3): 1055-66.
30. Klausner, E. A., Lavy E., Friedman, M., Hoffman, A., (2003)
8. S.J. Hwang, H Park and K Park, ―Gastric Retentive Drug Delivery Expandable gastroretentive dosage forms. J. Control. Release 90, 143–
Systems,‖ Critical Reviews in Therapeutic Drug Carrier Systems, 15 162.
(3) (1998), pp. 243-284.
31. Garg R., Gupta G.D. (2008) Progress in Controlled Gastroretentive
9. Swetha S, Allena RT and Gowda DV: A comprehensive review on Delivery Systems. Trop. J. Pharm. Res., 7 (3): 1055-1066
gastroretentive drug delivery systems. International Journal of
Pharmaceutical and Biomedical Research 2012; 3:1285-1293. 32. Hoffman A. (1998) Pharmacodynamic aspects of sustained release
preparation. Adv. Drug [Link]. 33: 185-199.
10. Kawatra M, Jain U and Ramana J: Recent advances in floating
microspheres as gastro-retentive drug delivery system: A review. 33. Hoffman A., Stepensky D. (1999) Pharmacodynamic aspects of modes
International Journal of Recent Advances in Pharmaceutical Research of drug administration for optimization of drug therapy. Crit. Rev.
2012; 2:5-23. Ther. Drug carrier Syst. 16: 571-639.
11. More, S., Gavali, K., Doke, O., Kasgawade, P. (2018). Gastroretentive A. Badoni , A. Ojha, G. Gnanarajani, P. Kothiyali; Review on Gastro
drug delivery system. Journal of Drug Delivery and Therapeutics, 8 Retentive Drug Delivery System; The Pharma Innovation, 2012;1(8):
(4), 24–35. doi: [Link] 32-42.
12. Klausner EA, Lavy E, Friedman M, et al. Expandable gastroretentive 34. Streubel A, Siepmann J, Bodmeier R, Floating Microparticles Based on
dosage forms. J Control Release 2003;90:143– 162. Low Density Foam Powder, Int. J. Pharm, 2002, 241, 279-N 292.
13. Laulicht B, Tripathi A, Schlageter V, et al. Understanding gastric 35. Kale R, Rao BS, Sharm S, Ramanmurthy KV, Preparation and
forces calculated from high-resolution pill tracking. ProcNatlAcadSci Evaluation of Floatable Drug Delivery System of Ketorolac
U S A 2010;107:8201–8206. Tromethamine, Int. J. Pharm, 2001, 64- 65.
14. Talukder R, Fassihi R. Gastroretentive delivery systems: a mini review. 36. Muthuamy K, Govindarajan G, Ravi TK, Preparation and Evaluation
Drug DevInd Pharm 2004;30:1019–1028. of Lansoprazole Floating Micropellets, Indian J. Pharm. Sci, 2005,
67(1), 75-79.
15. Gutierrez-Rocca J, Omidian H, Shah K. Progresses in gastroretentive
drug delivery systems. Bus Brief Pharmatech 2003;15:3–6. 37. Streubel A, Siepmann J, Bodmeier R, Floating Microparticles Based on
Low Density Foam Powder, Int. J. Pharm, 2002, 241, 279- 292.
16. Anne Waugh and Allison Grant. The digestive system: Stomach-
Functions of stomach. Ross ans Wilson anatomy and physiology in 38. Streubel A, Siepmann J, Bodmeier R. Floating Matrix Tablets Based
health and [Link] by Elsiver Publications. 2014; 12th Edition: on Low Density Foam Powder, Effects of Formulation and Processing
301. Parameters on Drug Release, Eur. J. Pharm. Sci, 2003, 18, 37-45.

ISSN: 2320-4850 [93] CODEN (USA): AJPRHS

Patole et al Asian Journal of Pharmaceutical Research and Development. 2023; 11(4): 79-94

39. Gaba P, Gaba M, Garg R and Gupta GD, Floating Microspheres, A 53. Hanif M, Abbas G. pH-responsive alginate-pectin polymeric rafts and
Review. [Link], 2008, 6(5), 121 123. their characterization. AdvPolym Technol. 2018; 37(5):1496– 506.
Available from: [Link]
40. Streubel A, Siepmann J, Bodmeier R, Floating Microparticles Based on
Low Density Foam Powder, Int. J. Pharm, 2002, 241, 279- 292. 54. R. Varges P, M. Costa C, S. Fonseca B, F. Naccache M, de Souza
Mendes P. Rheological characterization of carbopol® dispersions in
41. Streubel A, Siepmann J, Bodmeier R. Floating Matrix Tablets Based water and in water/glycerol solutions. Fluids [Internet]. 2019; 4(1):3.
on Low Density Foam Powder, Effects of Formulation and Processing Available from: [Link]
Parameters on Drug Release, Eur. J. Pharm. Sci, 2003, 18, 37-45.
55. Panda M, Rao MEB, Patra CN, Panda J, Panigrahi KC, Patro G.
42. Singh BN, Kim KH, Floating Drug Delivery Systems: An Approach to Formulation and development of floating multiple-unit minitablets of
Oral Controlled Drug Delivery Via Gastric Retention, J. Control. Rel, Nimodipine without using a gas-generating agent: in vitro and in vivo
2000, 63, 235-259. characterization. Futur J Pharm Sci. 2020; 6(1). Available from:
43. Heng WS, Wong TW, Melt Processes for Oral Solid Dosage Forms, [Link]
Pharm Tech, 2003, 1-6. 56. Lalge R, Thipsay P, Shankar VK, Maurya A, Pimparade M, Bandari S,
44. Chokshi R, Zia H, Hot Melt Extrusion Technique, A Review, Iranian J et al. Preparation and evaluation of cefuroxime axetilgastroretentive
Pharm Res, 2004, 3: 3-16. floating drug delivery system via hot melt extrusion [Link] J
Pharm. 2019; 566:520–31. Available from:
45. Breitenbach J., Melt Extrusion: From Process to Drug Delivery [Link]
Technology, Eur J Pharm Biopharm, 2002, 54: 107 – 117.
57. Li Q, Guan X, Cui M, Zhu Z, Chen K, Wen H, et al. Preparation and
46. Kidokoro M, Sasaki K, Haramiishi Y, Matahira N, Effect of investigation of novel gastro-floating tablets with 3D extrusionbased
Crystallization Behaviour of Polyethylene Glycol 6000 on the printing. Int J Pharm [Internet]. 2018; 535(1–2):325–32. Available
Properties of Granule Prepared by Fluidized Hot Melt Granulation from: [Link]
(FHMG), Chem Pharm Bull, 2003, 51 (5): 487 – 493.
58. Panda S, Sailada NS, Devi B, Pattnaik S, Maharana L. Design of
47. Parashar AK, Patel P, Gupta A, Jain N, Kurmi B. Synthesis floating drug delivery systems: An update on polymeric advancements
Characterization and in vivo Evaluation of PEGylated PPI Dendrimer with special reference from natural origin. Int. J. Pharm. Sci. Rev. Res.
for Safe and Prolonged Delivery of Insulin. Drug Del Letters. 2019; 9: 2016; 39:125–132.
248-63.
59. Jose G R, Omidian H, Shah K. Progress In Gastroretentive Drug
48. Ghori MU, Grover LM, Asare-Addo K, Smith AM, Conway BR. Delivery Systems, Pharm. Tech., 10th edition, 2003, 152-154.
Evaluating the swelling, erosion, and compaction properties of
cellulose ethers. Pharmaceutical Development and Technology. 2017; 60. Yen MK, Jenkins PG, Davis SS, Combs GA, Improvement of Delivery
(2):183–97. Capabilities of Microparticle Systems using Blend of Poly (D, L-
Lactate Co-Glycoside) Poly (Ethylene Glycol), J ContRel, 1995, 37, 1-
49. Zubedi SS, Mohammed S. Floating Tablets and its Polymers. Journal 9.
of Drug Delivery and Therapeutics. 2018; 8(5-s):16–24.
61. Shimpi S, Chauhan B, Mahadik KR, Paradkar P, Preparation and
50. Sharma D, Sharma A. Gastroretentive drug delivery system - a mini Evaluation of Diltiazem Hydrochloride-Gelucire 43/01 Floating
review. Asian Pacific Journal of Health Sciences. 2014; (2):80–9. Granules Prepared by Melt Granulation, AAPS Pharmscitec, 2004,
5(3), Article 43.
51. Jafar M, Alghamdi HS, Khalid MS, Al-Hussain MJ, Alghamdi SA,
Alahamad ZY, Almoumen AM. Enhanced analgesic activity and 62. Chen J, Blevins WE, Park H, Park K, Gastric Retention Properties of
reduced gastric ulceration potential of ibuprofen sodium through a Superporous Hydrogel Composites, J Con Rel, 2000, 64, 39-51.
novel bouyant In Situ gelling system. Lat. Am. J. Pharm. 2019,
38:599–608. 63. Deshpande A A, Rhodes C T, Shah N H. Controlled release drug
delivery system for prolonged gastric residence: an overview,‖ Drug
52. Kim H, Lee CL, Lee S, et al. Mechanically robust gastroretentive drug- Dev. Ind. Pharm, 22(6), 1996, 531- 539.
delivery systems capable of controlling dissolution behaviors of
coground β lapachone. Pharmaceutics.2019, 11. 64. Desai S, Bolton S. A floating controlled release drug delivery system:
in vitro- in vivo evaluation, Pharm Res, 10(9), 1993, 1321-1325.

ISSN: 2320-4850 [94] CODEN (USA): AJPRHS