ABSTRACT

The purpose of writing the review on gastroretentive drug delivery systems (GRDDS) was to
accumulate the current literature with a special emphasis on several gastroretentive approaches that
have recently become important methodologies in the field of site-specific orally administered
sustained/controlled release drug delivery. Technological efforts have been made in research and
development of rate-controlled oral drug delivery systems to solve physiological difficulties, like short
gastric residence times (GRT) and unpredictable gastric emptying times (GET). GRDDS are an
approach to prolong the GRT, thereby targeting site-specific drug release in the upper gastrointestinal
tract (GIT) for local or systemic effect. Conventional oral dosage forms pose low bioavailability
problems because of their quick gastric transition from the stomach, particularly in case of drugs that
are less soluble at an alkaline pH of the intestine. Also, drugs that produce their local action in the
stomach get quickly emptied and don’t get sufficient residence time in the stomach. Several efforts
have been made to extend the retention time of drug delivery system to reduce the frequency of dose
administration. GRDFs not only prolong dosing intervals, but also increase patient compliance beyond
the level of existing controlled release dosage forms. This article gives an overview on advantages,
disadvantages and characterization of gastroretentive drug delivery systems. This review also includes
commercially available gastroretentive products and patents.

INTRODUCTION

The oral delivery of drugs is the most favoured route of administration because of ease of
administration. Drug bioavailability of oral dosage forms is subjective by various factors. One of the
significant factor is a gastric residence time (GRT) of these dosage forms. Truly, gastric retention has
received important interest in the past few years as many of the conventional oral delivery systems
have some limits related to fast gastric emptying time. Gastroretentive dosage form is a type of novel
drug delivery system which can persist in the stomach for prolonged period of time and thus increases
the GRT of drugs. Gastro-retention helps to improve bioavailability of drugs.

The classification of different modes of gastric retention:

- High-density (Sinking) systems

- Low-density (Floating) systems
- Expandable systems
- Superporous hydrogel systems
- Mucoadhesive systems
- Magnetic systems

The conventional drug delivery system achieves and also maintained the drug concentration in the
therapeutically effective range desired for treatment, only when taken numerous times a day. A drug
that has a narrow absorption window in the GIT may have poor absorption. For these drugs, GRDDS
offer the advantages in extending the gastric emptying time.

Many problems are faced in preparing controlled release systems for better absorption and improved
bioavailability. Drug absorption from the GIT is a complex process and is subject to several variables.
It is broadly recognized that the extent of GIT drug absorption is correlated to contact time with small
intestinal mucosa. GRDDS can persist in the GI region for many hours and therefore significantly
extend the GRT of drugs. Extended gastric retention increases bioavailability, decreases drug waste
and increases solubility of drugs which are less soluble in high pH environment. To prepare a
successful stomach specific or a gastroretentive DDS, numerous techniques are presently used like
hydrodynamically balanced systems (HBS)/ floating drug delivery system, low density system, raft
systems incorporating alginate gels, mucoadhesive or bioadhesive systems, high density systems,
super porous hydrogelsand magnetic systems. Current progress in technology has provided feasible
dosage alternatives which can administered by different routes of administration like oral, topical,
parenteral, rectal, nasal, ocular, vaginal, etc. But out of all these routes, oral route is considered as
the best preferred and practiced way of drug delivery, due to the following reasons:

- Ease of administration
- Ease of production
- More flexibility in designing
- Low cost

Many drugs given by oral route are subjected to absorption through the GIT, with major absorption
from the stomach and intestine. Drugs, which is absorbed from the stomach or show local effect,
should spend extreme time in stomach. This is found very hard to happen, in case of the conventional
dosage forms such as capsules and tablets, due to the gastric emptying. Gastric emptying of dosage
form depends on several factors like temperature and viscosity of the meal, volume and composition
of the meal, emotional state of the individual, the pH of the stomach, body posture, etc. Prolonged
gastric retention of the drug is required in the following conditions:

- The drug is best absorbed from the stomach. E.g., Aspirin, Phenylbutazone, etc.
- Slow dissolving drugs.
- Dissolution and absorption of drug is stimulated by the food. E.g., Griseofulvin.
- Drug show local effects within the stomach.
- Gastric fluids facilitate and increase the disintegration and dissolution of the drug.

In order to achieve all these situations, various methods of the controlled drug delivery have been
established. One of these types of the methods, which ensure that a particular drug/dosage form
remains in the stomach for longer duration of time, is GRDDS.

However, in following condition gastroretention is considered undesirable:

- For gastro irritant drugs.
E.g., Diclofenac sodium, Ibuprofen, Acetylsalicylic acid, etc.
- For acid labile drugs that are stable at gastric pH.
E.g., Macrolide antibiotics
- Drugs which get absorbed throughout the GIT equally.

STOMACH -AN OVERVIEW

The stomach is J shaped enlargement of GIT directly inferior to the diaphragm in epigastric, umbilical
and left hypochondriac regions of the abdomen. It connects esophagus to the duodenum, the first part
of the small intestine and provides a barrier to the delivery of drugs to the small intestine.

Anatomy of stomach:

The stomach has four regions:

(1) Cardia (2) Fundus (3) Body (4) Pylorus

Figure 1. Anterior view of regions of stomach

Gastric emptying:

The process of gastric emptying happens both during fasting and fed state. In the fasted state, it is
categorized by an interdigestive cycle both through the stomach and small intestine, every 2-3 hours.
This activity is called the interdigestive myoelectric cycle or migrating myoelectric complex (MMC). It
is composed of four phases (Figure 2).

Phase Duration

Phase-I 30-60 min with infrequent contractions

(Basal phase)

Phase-II 20-40 min with the irregular action potential and contractions as the phase
developments, the intensity and the frequency also rises gradually
(Preburst phase)

Phase-III 10-20 min, it contains intense and regular contractions for short periods.
It’s due to this wave that all the undigested material is swept from stomach
(Burst phase)
to the small intestine

Phase-IV 0-5 min and happens between phase three & one of two successive cycles

Figure 2. Gastrointestinal motility patterns

After the digestion of mixed meal, the pattern of contractions changes from fasted to fed state. This is
also recognized as digestive motility pattern and contains endless contractions as in phase II of fasted
state. The contractions result in decreasing the size of food particles (<1 mm), which are propelled
towards the pylorus in the suspension form. Throughout the fed state onset of mmc is postponed
resulting in a slowdown of the gastric emptying rate. Scintigraphic studies including the measurements
of the gastric emptying rate in healthy human subjects have discovered that an orally administered
controlled release dosage form is primarily subject to two physiological difficulties:
1. Short GRT
2. Unpredictable gastric emptying rate

Yet additional major difficulty encountered through the oral route is first pass effect that leads to
decreased systemic bioavailability of numerous drugs.
GASTRORETENTIVE DRUG DELIVERY SYSTEMS

Drugs which are easily absorbed from the gastrointestinal tract and those with short half-lives are
quickly eliminated from the systemic circulation due to which frequent dosing is required. To overcome
this problem, gastroretentive drug delivery systems which provide effective plasma drug concentration
for longer periods thereby reducing the dosing frequency are being formulated. It also has an
advantage of minimizing the fluctuations in plasma drug concentration by delivering the drug in a
controlled and reproducible manner. If the drugs are poorly soluble in intestine because of alkaline pH,
gastric retention may improve the solubility before they emptied resulting in GI absorption of drugs
with narrow therapeutic absorption window and also monitoring the release of drugs that have site
specific-absorption limitation. Drugs that might take benefit of gastric retention contain the drugs
whose solubility is fewer in the higher pH of the small intestine than stomach (E.g., Cinnarizine,
Chlordiazepoxide, etc.), the drugs prone to degradation in intestinal pH (E.g., Captopril), and drugs for
local action in stomach (E.g., Misoprostol). Sedatives, antibiotics, catecholamines, anticonvulsants,
analgesics, anti-hypertensives, vitamins and muscle relaxants can also be administered in
hydrodynamically balanced systems (HBS) dosage form (Figure 3).

Gastroretentive drug delivery systems extend the dosing intervals and therefore improve patient
compliance. The presence of drug in solution form is an important requisite for the drug to get
absorbed. But, if the drug solubility is poor, the time required for drug to dissolve within stomach will
be high and transit time becomes most severe factor, which might consequently affect the absorption
of the drug. So, dose of administration of such drugs should be kept at repeated intervals in a single
day. However, other formulations/novel dosage forms like liposome, nanoparticle, microspheres, etc.
can also use for controlled release effect, but GRDDS is considered more desirable alternative for
improved absorption through the stomach.

Figure 3.Techniques of GRDDS

FACTORS AFFECTING GASTRIC RETENTION

 1. Density:Gastric retention time (GRT) is a function of dosage form buoyancy which is
dependent on the density. The density of the dosage form must be lower than the gastric
contents (1.004 gm/ml).
2. Size:Dosage form units having a diameter of greater than 7.50 mm are stated to have an
improved GRT related with those having a diameter of 9.90 mm.
3. Shape of the dosage form:Tetrahedron and ring shaped devices having a flexural modulus
of 48 and 22.50 kilo pounds per square inch are reported to have a better GRT at 24 hours
compared with other shapes.
4. Single or Multiple unit formulation: Multiple unit formulations show a more expectable
release profile and insignificant damaging of performance because of failure of units, allow co-
administration of units that have dissimilar release profiles related with single unit dosage
forms.
5. Fed/Unfed state:In fasting conditions, gastrointestinal motility is categorized by periods of
strong motor activity that occurs every 1.5 to 2 h and if timing of administration of the
formulation overlaps with that of the MMC, the gastric retention time of unit can be anticipated
to be very short. However, in fed state, MMC is postponed and gastric retention time is
significantly longer.
6. Nature of meal: Feeding of fatty acid salts or indigestible polymers can modify the motility
pattern of stomach to a fed state, hence reducing the gastric emptying rate.
7. Caloric content:GRT can be improved by 4 to 10 h with a meal which is high in proteins and
fats.
8. Age: Elderly people, mostly those over 70 years, have a significantly longer gastric retention
time.
9. Frequency of feed: Gastric retention time can rise by over 400 minutes, when consecutive
meals are given related with a single meal because of the low frequency of MMC.
10. Gender: Mean ambulatory gastric retention time in males (3.4 ± 0.6 hours) is less correlated
with their age and race matched female counterparts (4.6 ± 1.2 hours), regardless of the
weight, body surface and height.
11. Posture: Gastric retention time can be differing between supine and upright ambulatory
states of patients.
12. Concomitant drug administration: Anticholinergics like atropine and propentheline increase
the GRT. Metoclopramide and Cisapride decrease GRT.
13. Disease state: Gastric ulcer, diabetes and hypothyroidism increase the GRT. Hyperthyroidism
and duodenal ulcers decrease the GRT.

ADVANTAGES OF GASTRORETENTIVE DRUG DELIVERY SYSTEMS

- Maintenance of constant therapeutic level over longer period of time.

E.g. Beta lactams antibiotics.

- Enhanced bioavailability of drugs.

E.g. Enhancement of bioavailability of controlled release gastroretentive dosage forms (CR-
GRDF) of riboflavin in comparison of non CR-GRDF polymeric formulation.

- Gastroretentive dosage form improves patient compliance by decreasing dosing frequency.

- Minimizing mucosal irritation of drugs, by releasing drug slowly at a controlled rate.
E.g. NSAIDs

- Treatment of GI disorders like GERD, Helicobacter pylori infection, etc.

- Floating drug delivery system is a feasible approach for the drugs that have limited
absorption in the intestine.

- The floating drug delivery system can reduce the counter activity of body, leading to higher
drug efficiency.

- For drugs that have comparatively short half-life, sustained release may result in a flip-flop
pharmacokinetics.
 - The floating drug delivery systems are beneficial for drugs that are absorbed through
stomach.
E.g. Antacids, Ferrous salts, etc.

- Sustained release drug delivery system reduces dosing frequency of drugs with short half-
life.

- Bioavailability enhances despite the first pass effect as a result of variations in plasma drug
concentration are escaped; a required plasma drug concentration is retained by the continuous
drug release.

- Controlled drug delivery of drugs.

DISADVANTAGES OR LIMITATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEMS

- Drugs, that undergo significant first pass metabolism, are not desirable candidate.

- Drugs having solubility or stability problems in the highly acidic gastric environment cannot be
formulated as GRDDS

- For swellable systems, the dosage forms must maintain size larger than the aperture of the resting
pylorus for the required time period.

- These systems do not offer important advantages over the conventional dosage forms of drugs,
which are absorbed throughout the gastrointestinal tract.

- Some drugs cause irritation to the gastric mucosa.

- The dosage form must be taken with a full glass of water.

- Violent gas generation, disintegration of dosage forms, burst release, dose dumping, and alkaline
microenvironment are the limitation for floating drug delivery.

- Patients cannot be dosed these formulations just before going to bed.

- It is effective only when the fluid level in the stomach is sufficiently high.

- However, as the stomach empties and the dosage form is at the pylorus, the buoyancy of the dosage
form may be impeded.

- The major challenge for a bioadhesive system is the high turnover rate of gastric mucus. There is
also the possibility of esophageal binding with bioadhesive drug delivery systems. The Hydrogel based
swelling system takes longer time to swell.

CRITERIA FOR SELECTION OF DRUG CANDIDATE FOR GRDDS

The gastro retentive drug delivery systems are suitable for following types of drug therapy:
- Absorption from upper GIT: Drugs have a particular site for maximum absorption.
Example: Ciprofloxacin
- Drug having low pKa, which remains unionized in stomach for better absorption.
- Drugs having a reduced solubility at higher pH.
Example: Captopril
- Local action as it is seen in the treatment of H. pylori by Amoxicillin trihydrate as in case of ulcers.
The bioavailability of drugs that get degraded in alkaline pH can be increased by formulating gastro
retentive dosage forms.
Example: Doxifluridine; which degrades in the small intestine.
- To minimize gastric irritation this may be caused by the sudden increase of drug concentration in
the stomach.
Example: NSAIDs
- Drugs that act locally in the stomach.
Example: Antacids, Antibiotics for bacterially based ulcers
- Drugs that are absorbed primarily in the stomach.
Example: Albuterol
- Drugs that are poorly soluble in alkaline pH.
- Drugs that have a narrow window for absorption, i.e., Drugs that are absorbed mainly from the
proximal part of small intestine.
Example: Riboflavin, Levodopa.
- Drugs that are absorbed rapidly from the GI tract.
Example: Amoxicillin.

NEED OF GASTRORETENTIVE DRUG DELIVERY SYSTEMS

Oral dosage forms pose low bioavailability problems because of their fast gastric transition from the
stomach, particularly in case of drugs that are less soluble at an alkaline pH of the intestine. Also the
drugs that produce their local action in the stomach get quickly emptied and do not get sufficient
residence time in the stomach. Therefore, frequency of dose administration in such condition is
increased. To avoid such problem floating drug delivery system has been developed.

APPROACHES FOR GRDDS

The different approaches established for formulating dosage form to produce a satisfactory gastric
retention and release within gastric region, are as follows:
- High-density system
- Floating system
- Hydrodynamically balanced system
- Gas-generating system
- Raft-forming system
- Low-density system
- Expandable system
- Super porous hydrogels
- Mucoadhesive or bioadhesive system
- Magnetic system
- Self-unfolding systems

STOMACH SPECIFIC FLOATING DRUG DELIVERY SYSTEM

Stomach specific FDDS has a bulk density lesser than gastric fluids and therefore remain buoyant in
the stomach without altering the gastric emptying rate for a longer period of time. However, the
system is float on gastric contents, the drug is released gradually at a preferred rate from the system.
After releasing drug, the residual system is emptied from stomach. It results in an increased gastric
residence time and a better control of variations in plasma drug concentration. The floating SRDF
present most of the characteristics of hydrophilic matrices and called ‘hydrodynamically balanced
systems’ (HBS) as they are able to preserve their low apparent density, however the polymer
hydrates and builds a gelled barrier on the outer surface. The drug is released gradually from the
swollen matrix, as in case of conventional hydrophilic matrices. These forms are anticipated to remain
buoyant (3-4 hrs) on the gastric contents without altering the intrinsic rate of emptying because their
bulk density is lesser than that of the gastric contents. Amongst the different hydrocolloids suggested
for floating form formulations, cellulose ether polymers are common, particularly hydroxyl propyl
methyl cellulose (HPMC). A fatty material with bulk density <1 may be added to the formulation to
increase the buoyancy and reduce the water intake rate.
Similar to formulation studies, research has been take on humans and animals to evaluate intragastric
retention performances of floating forms. These calculations were realized either directly by gamma
scintigraphic and X-ray monitoring of the form transit in the GIT or indirectly by pharmacokinetic
studies with drug tracer.

MECHANISM OF FLOATING DRUG DELIVERY SYSTEM

While the system is floating on the stomach, the drug is released gradually at the desired rate from
system. After releasing drug, the residual system is flattened from the stomach besides a minimal
gastric content needed to permit suitable attainment of the buoyancy retention principle, a minimal
level of floating force (F) is also essential to retain dosage form constantly buoyant on surface of the
meal. The apparatus used to measure the floating force kinetics operates by measuring continuously
the force equivalent to F (as a function of time) that is mandatory to main submerged object. If F is
on the higher positive side, object floats better. The apparatus helps in optimizing floating drug
delivery system with respect to stability and durability of floating forces formed in order to stop the
problems of unexpected intragastric buoyancy capability variations (Figure 4).

Figure 4. Mechanism of floating system, GF = Gastric Fluid

F = F Buoyancy - F Gravity
= (Df-Ds) × gv --- (1)
Where; F = Total vertical force, Df = Fluid density, Ds = Object density, g = Acceleration due to
gravity, v = Volume

CLASSIFICATION OF FDDS BASED ON THE MECHANISM OF BUOYANCY

A. Single Unit Floating Dosage Systems

(a) Effervescent Systems

(b) Noneffervescent Systems

B. Multiple Unit Floating Dosage System

 (a) Noneffervescent Systems
(b) Effervescent Systems
(c) Hollow Microspheres

C. Raft-Forming Systems

[A] SINGLE UNIT FLOATING DOSAGE SYSTEMS

(a) Effervescent Systems (Gas-generating Systems):

These systems used matrices prepared with swellable polymers such as polysaccharides like
chitosan, HPMC, citric acid and tartaric acid, effervescent components like sodium bicarbonate or
chambers containing liquid that gasifies at body temperature. The optimum stoichiometric ratio of
sodium bicarbonate and citric acid for gas generation is described to be 1:0.76. The commonest
approach for preparing these systems contains resin beads loaded with bicarbonate and coated with
ethyl cellulose. The coating, that is insoluble but permeable, allows permeation of water. So, Co 2 is
released, causing the beads to float in stomach.
Excipients used in these systems include Carbopol®, polyacrylate polymers, HPMC, polyvinyl acetate,
sodium alginate, polyethylene oxide, agar, polycarbonates and calcium chloride.

b) Non-effervescent Systems:
These types of systems, after swallowing, swell unrestrained via imbibition of gastric fluid to a level
that it stops their exit from stomach. The systems can be discussed as ‘plug-type systems’ as they
have a tendency to persist lodged near pyloric sphincter. One of the formulation approaches of such
dosage forms contains the mixing of drug and gel that swells in contact with GI fluid after oral
administration and keeps a relative integrity of shape and a bulk density <1 within outer gelatinous
barrier. The air surrounded by swollen polymer discusses buoyancy to these dosage forms. E.g.,
Colloidal gel barrier, micro porous compartment system, alginate beads and hollow microspheres.
Additional type is fluid-filled floating chamber that comprises addition of a gas-filled floatation
chamber into micro porous component that houses a drug reservoir. Apertures are present along the
top and bottom walls through which the GI fluid enters to dissolve drug. Other two walls in contact
with fluid are sealed therefore the undissolved drug stay therein. The fluid present could be air, under
partial vacuum or any other appropriate solid, liquid or gas having an appropriate specific gravity and
an inert behaviour. The device is of swallowable size, remains afloat in stomach for longer period of
time, and after the complete release shell disintegrates, passes off to intestine and eliminated (Figure
5).

Figure 5. Gas filled floatation chamber

[B] MULTIPLE UNIT FLOATING DOSAGE SYSTEMS:

In spite of intensive research and development in the area of hydrodynamically balanced system and
other floating tablets, these systems undergo a significant drawback of the high variability of GI
transit time, when orally administered, due to their all or nothing gastric emptying nature. With the
intension to solve the above difficulty, multiple unit floating systems were established, that decrease
the inter-subject variability in absorption and reduce the chance of dose dumping. Reports are
obtained in the development of both effervescent and non-effervescent multiple unit systems. Much
research has been intensive and the scientists are still discovering the field of hollow microspheres,
able to float on gastric fluid and having better GI retention properties.

(a)Non-effervescent Systems:

No far report was found in literature on non-effervescent multiple unit systems, when
compared with effervescent systems. Though, few workers have described the probability of
developing such system comprising Indomethacin, by using chitosan as polymeric excipient. A
multiple unit hydrodynamically balanced system comprising Indomethacin as a model drug
produced by extrusion method is described. A mixture of drug, acetic acid and chitosan is
extruded through a needle, and extrudate is cut and dried. Chitosan hydrates floats in acidic
media, and required drug release could be achieved by altering drug-polymer ratio.

b) Effervescent Systems (Gas-generating Systems):

Ikura et al.described sustained release floating granules comprising tetracycline hydrochloride. The
granules are the mixture of drug granulates of two stages A and B (A contains 60% of HPMC, 40% of
polyacrylic acid and 20% of the drug and B contains 70% of sodium bicarbonate and 30% of tartaric
acid). 60% by weight of granules of stage A and 30% by weight of granules of stage B are mixed with
a lubricant and packed into capsules. In dissolution media, the capsule shell dissolve and liberate the
granules, that showed a floating time of more than 8 hrs and sustained drug release of 80% in about
6.5 hrs. Floating minicapsules of pepstatin that have a diameter of 0.1-0.2 mm has been described by
Umezawa.

Figure 6. (A) Multiple-unit oral floating drug delivery system

(B) Mechanism of floatation via Co2 generation

These mini capsules comprise a central core and a coating. The central core comprises of a
granule composed of lactose, sodium bicarbonate and a binder that is coated with HPMC. Pepstatin is
coated on top of HPMC layer. The system floats due to the release of carbon dioxide in gastric fluid
and pepstatin exist in the stomach for longer periods (Figure 6)

c) Hollow Microspheres:

Hollow microspheres are regarded as the most promising buoyant systems, as they’ve exclusive
advantages of multiple unit systems and also better floating properties, due to central hollow space
inside microsphere. The general methods involved in their preparation contain simple solvent
evaporation, solvent diffusion & evaporation. The drug release and better floating properties generally
depend on plasticizer, type of polymer and solvents employed for preparation. Polymers like cellulose
acetate and Eudragit were used in preparation of hollow microspheres, and drug release can be
moderated by enhancing polymer quantity and polymer plasticizer ratio.

[C] RAFT FORMING SYSTEMS:

These systems have established much attention for delivery of antacids and drug delivery for GI
disorders and infections. The mechanism complied in the raft formation contains the development of
viscous cohesive gel in contact with GI fluids, in which each portion of liquid swells forming a
continuous layer known as raft. The raft floats on gastric fluids due to low bulk density produced by
the development of Co2. Generally, the system comprises a gel forming agent and alkaline carbonates
or bicarbonates liable for the development of Co2 to make the system fewer dense and float on the GI
fluids. Jorgen et al. defined an antacid raft forming floating system. The system comprises gel forming
agent, acid neutralizer and sodium bicarbonate that forms a foaming sodium alginate gel when in
contact with GI fluids. The raft thus formed, floats on GI fluids and stops the reflux of the GI contents
into the esophagus by acting as a barrier amongst the esophagus and stomach.

Table 1: COMPARISONS BETWEEN CONVENTIONAL AND GASTRORETENTIVE DRUG DELIVERY

SYSTEM [22]:

Parameters Gastroretentive Drug Conventional Drug Delivery

Delivery System System

Risk of toxicity Lower Higher

Patient compliance High compliance level Less compliance level

Dose dumping High risk No risk

Drugs Beneficial for drugs: Not beneficial for drugs:

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

Table 2

LIST OF DRUGS FORMULATED AS SINGLE AND MULTIPLE UNIT FORMS OF FLOATING DRUG DELIVERY
SYSTEMS [16]:

DOSAGE FORMS DRUGS

Floating microspheres Aspirin, p-nitroaniline, Griseofulvin, Ketoprofen, Ibuprofen, Verapamil

and Terfinadine

Floating Films Cinnarizine, p-Aminobenzoic acid, Prednisolone and Piretanide

Floating tablets and Acetaminophen, Isosorbide mononitrate, Ampicillin, Atenolol,

Pills Theophylline, p-aminobenzoic acid, Aspirin, Verapamil hydrochloride,
Sotalol

Floating Capsules Diazepam, Furosemide, Misoprostol, L-Dopa and Benserazide,

Pepstatin, Verapamil HCl and Nicardipine

Floating powders Riboflavin, Phosphate, Sotalol and Theophylline

Floating granules Diclofenac sodium, Indomethacin, Prednisolone, Cinnarizine,

Diltiazem, Fluorouracil and Isosorbide mononitrate
APPLICATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEMS

1) Enhanced Bioavailability:
Bioavailability of riboflavin controlled release gastroretentive dosage forms is significantly
improved compared to administration of non-controlled release gastroretentive dosage forms
polymeric formulations. There are numerous different procedures, related to absorption and
transit of drug in the GIT, which act concomitantly to impact the magnitude of drug
absorption. (Cook JD et al., 1990.

2) Sustained Drug Delivery:

Oral controlled release formulations are faced with problems like GRT in the gastrointestinal
tract. HBS systems can be used to overcome the problems that can remain in stomach for
prolonged period of time and have bulk density <1 as a result of which they can float on the
GI contents. The systems are comparatively large in size & passing from pyloric opening is
prohibited.

3) Site Specific Drug Delivery Systems:

These systems are frequently beneficial for drugs which are especially absorbed from stomach
or the proximal part of small intestine. The controlled/slow delivery of drug to the stomach
offers adequate local therapeutic levels and limits the systemic exposure to drug. This
decreases side effects that are produced by drug in blood circulation. Also, the extended
gastric availability of a site directed delivery system may reduce the frequency of dosing.
E.g., Furosemide and Riboflavin. (Menon A et al., 1994)

4) Absorption Enhancement:
Drugs that are having poor bioavailability due to site specific absorption from upper part of
the gastrointestinal tract are potential candidates to be formulated as FDDS, thus maximizing
their absorption. (Rouge N et al., 1998)

5) Minimized adverse activity at the colon:

Retention of drug in HBS systems at the stomach reduces the amount of drug that extents
the colon. Hence, undesirable activities of drug in the colon can be prohibited. This
pharmacodynamics aspect offers the rationale for gastroretentive dosage form for beta
lactam antibiotics which are absorbed only from small intestine, and whose presence in colon
leads to the growth of microorganism resistance.

6) Reduced fluctuations of drug concentration:

Constant input of drug following controlled release GRDF administration produces blood drug
concentrations within narrower range related to immediate release dosage forms. Hence,
fluctuations in drug effects are reduced and concentration dependent adverse effects that are
related with peak concentrations can be prohibited.

CONCLUSION

Development of an efficient gastroretentive dosage form for stomach specific drug delivery is
an actual challenge. Thus, to produce the preferred gastro retention several methods have
been used, out of which, the floating drug delivery system has emerged as the best promising
method. These systems provide the benefit of better absorption of drugs that are absorbed
from upper part of stomach. Local action of drug is increased as the system rests in stomach
for longer time. This leads to less frequent dosing and enhanced efficiency of the treatment.
Good stability and better drug release as compared to other conventional dosage forms make
such system more reliable. Drug absorption in GIT is a highly variable procedure and
prolonging GI retention of the dosage form prolongs the time of drug absorption. Floating
drug delivery system promises to be a potential approach for gastric retention. Though there
are number of complications to be worked out to achieve extended GI retention, many
companies are focusing toward commercializing this method.

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