IAJPS 2016, 3 (9),1020-1024

Navya and A.Madhu Babu

CODEN (USA): IAJPBB

ISSN 2349-7750

ISSN: 2349-7750

INDO AMERICAN JOURNAL OF

PHARMACEUTICAL SCIENCES
Available online at: http://www.iajps.com

Review Article

FLOATING MICROSPHERES FOR GASTROINTESTINAL

DISORDERS
J.Navya, A.Madhu Babu.
Comprime Labs,chitanyapuri,Hyderabad,Telangana,India.
Abstract:
Drug absorption in the gastrointestinal tract is a highly variable process. Floating microspheres are promises
to be a potential approach for gastric retention enhances the bioavailability and controlled delivery of various
therapeutic agents. Significant attempts have been made worldwide to explore these systems according to
patient requirements, both in terms of therapeutic efficacy and compliance. Floating microspheres as gastro
retentive dosage forms precisely control the release rate of target drug to a specific site and facilitate an
enormous impact on health care. These systems also provide tremendous opportunities in the designing of new
controlled and delayed release oral formulations, thus extending the frontier of futuristic pharmaceutical
development. Furthermore, recent innovations in pharmaceutical investigation will surely provide real
prospects for establishment of novel and effective means in the development of these promising drug delivery
systems.
Keywords: Gastro Retention, Hollow microspheres, Floating microspheres, Short halflife, Solvent Diffusion,
Floating drug delivery system (FDDS).

Corresponding author:
A.Madhu Babu.
Comprime Labs,
chitanyapuri,
Hyderabad,Telangana,India.

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Please cite this article in press as Navya and A.Madhu Babu, Floating Microspheres for Gastrointestinal
Disorders, Indo Am. J. P. Sci, 2016; 3(9).

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IAJPS 2016, 3 (9),1020-1024

Navya and A.Madhu Babu

INTRODUCTION:
Gastroretentive Drug Delivery System: Oral
controlled release (CR) dosage forms (DFs) have
been developed over the past three decades due to
their considerable therapeutic advantages such as
ease of administration, patient compliance and
flexibility in formulation. However, this approach
is bedilled with several physiological difficulties
such as inability to restrain and locate the
controlled drug delivery system within the desired
region of gastrointestinal tract (GIT) due to
variable gastric emptying and motility [1-4].
Furthermore, the relatively brief gastric emptying
time (GET) in humans which normally averages 23 h through the major absorption zone, i.e.,
stomach and upper part of the intestine, can result
in incomplete drug release from the drug delivery
system leading to reduced efficacy of the
administered dose. Therefore, control on placement
of a variety of important drugs through
appropriately designed drug delivery system (DDS)
in a specific region of the GI tract offers
advantages particularly for those having a narrow
absorption window in the GIT or those with
stability problems. These considerations have led to
the development of a unique oral controlled release
dosage form with Gastroretentive properties. After
oral administration, such a DF would be retained in
the stomach and release the drug there in a
controlled and prolonged manner so that the drug
could be supplied continuously to its absorption
sites in the upper gastrointestinal tract.
Gastroretentive dosage form can remain in the
gastric region for several hours and hence
significantly prolong the gastric residence time of
drugs. Prolonged gastric retention improves
bioavailability, reduces drug waste and improves
solubility of drugs that are less soluble in a high pH
environment. It is also suitable for local drug
delivery to the stomach and proximal small
intestine [6-10].
Gastric emptying is a complex process, one that is
highly variable and that makes in vivo performance
of drug delivery systems uncertain. A controlled
drug delivery system with prolonged residence time
in the stomach can be of great practical importance
for drugs with an absorption window in the upper
small intestine. Floating or hydrodynamically
controlled drug delivery systems are useful in such
applications. Various gastroretentive dosage forms
are available, including tablets, capsules, pills,
laminated films, floating microspheres, granules
and powders. The dosage form comprises a
plurality of buoyant particles, each comprising an
inner drug-containing core, an intermediate layer
surrounding said core and a release rate-controlling

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ISSN 2349-7750

outer coating. Floating microspheres have been

gaining attention due to the uniform distribution of
these multiple-unit dosage forms in the stomach,
which results in more reproducible drug absorption
and reduced risk of local irritation.

Figure 1: Drug blood level versus time profiles

Mechanism:
Most of the floating systems are single-unit
systems, which are generally unreliable and nonreproducible in prolonging the GRT, in virtue of
their unpredictable all-or-nothing emptying
process. On the other hand, multiple-unit dosage
forms appear to be better suited, since they claim to
reduce inter-subject variability in absorption and
have a lower dose-dumping probability. The
uniform distribution of these multiple unit dosage
forms along the GIT could result in more
reproducible drug absorption and reduced risk of
local irritation; this gave way to the development of
gastroretentive floating microspheres [11-13]
Floating microspheres are gastroretentive drug
delivery systems based on a non-effervescent
approach. Hollow microspheres, microballoons or
floating
microparticles
are
terms
used
synonymously for floating microspheres. Floating
microspheres are, in a strict sense, spherical empty
particles without a core. These are free-flowing
particles, with size ranging from 1 to 1000 m.
non-effervescent
hollow
polycarbonate
microspheres are developed by using an emulsion
solvent evaporation method. This gastrointestinal
transit-controlled preparation is designed to float on
gastric juice with a specific density of less than
one. This property results in delayed transit through
the stomach. The drug is released slowly at desired
rate, resulting in increased gastric retention with
reduced fluctuations in plasma drug concentration
[14].
Advantages of floating microspheres:
1. Bioavailability enhances, despite first pass
effect, because fluctuations in plasma drug
concentration are avoided, and a desirable plasma

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Navya and A.Madhu Babu

drug concentration is maintained by continuous

drug release.
2. Superior to single-unit floating dosage forms, as
such microspheres release drugs uniformly and
there is no risk of dose dumping.
3. Enhanced absorption of drugs that solubilise
only in stomach.
4. Site-specific drug delivery to the stomach can be
achieved.
5. Avoidance of gastric irritation, due to sustained
release effect.
6. Better therapeutic effect of short half-life drugs
can be achieved.
Disadvantage
Reproducibility of the particle size of the
formulation.
Methods
of
Preparation
of
Hollow
Microspheres:
Hollow microspheres are prepared through
the solvent diffusion and evaporation method to
create the hollow inner core. The solvent is
evaporated either by increasing the temperature
under pressure or by continuous stirring.
The floating microspheres are prepared by the
emulsion solvent diffusion method, utilizing enteric
acrylic polymers dissolved with drug in a mixture
of dichloromethane and ethanol. The above
solution was introduced in the aqueous solution of
polyvinyl alcohol at 40 C with constant stirring to
form an oil-in-water (o/w) emulsion. After
agitating the system for 1 hour, the resulting
polymeric particulate systems were sieved between
500 and 1000 mm and then dried overnight at 40 C
to produce hollow microspheres.
A novel two step manufacturing process of hollow,
poly-butyl-2-cyanoacrylate (PBCA) microspheres
in an aqueous phase was developed to synthesize
gas-filled
hollow
microspheres.
These
microspheres have an organic shell. The first step is
the
polymerization
process
of n-butyl-2cyanoacrylate (BCA) to form nanoparticles. During
the second step, the nanoparticles attach on a
microbubble precursor and finally form hollow
microspheres.
Cellulose acetate, chitosan, Eudragit, Acrycoat,
Methocel, polyacrylates, polyvinyl acetate,
Carbopol,
agar,
polyethylene
oxide,
polycarbonates, acrylic resins and polyethylene
oxide are some of the polymers used in the
preparation of hollow microspheres.
Mechanism
of
formation
of
hollow
microspheres
Ethanol and methanol have been found to be good
solvents for most drugs and polymers.
Dichloromethane and chloroform are good bridging

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ISSN 2349-7750

liquids due to the good linkage between the drug

and polymers and to their immiscibility in the
external
phase.
Water-insoluble
polymers,
mentioned above, show higher solubility in
dichloromethane than ethanol. However, ethanol
has higher solubility in water. As soon as the
polymer solution was added to the aqueous
medium, the ethanol diffuses rapidly from the
droplets of the polymer solution. Simultaneous
diffusion of water inside the sphere further
decreased the ethanol concentration, hence the
polymer precipitated, resulting in the formation of
microspheres. Dichloromethane remaining as the
central core diffused slowly due to its low water
solubility. Therefore, the diffusion of ethanol
played an important role in determining the size
and shape of the microspheres.

Mechanism of gastro retention

When microspheres come in contact with gastric
fluid, the gel formers, polysaccharides, and
polymers hydrate to form a colloidal gel barrier that
controls the rate of fluid penetration into the device
and drug release. As the exterior surface of the
dosage form dissolves, the gel layer is maintained
by the hydration of the adjacent hydrocolloid layer.
The air trapped by the swollen polymer lowers the
density and confers buoyancy to the microspheres.
However, a minimal gastric content is needed to
allow proper achievement of buoyancy.
Characterization/evaluation
microspheres

of

floating

Particle size
Size is measured using an optical microscope, and
mean particle size is calculated by measuring 200
300 particles with the help of a calibrated ocular
micrometer
Tapped density and compressibility index
The tapping method is used to determine the tapped
density and percentage compressibility index, as
follows

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Navya and A.Madhu Babu

ISSN 2349-7750

where V and Vo are the volumes of the sample after

and before the standard tapping, respectively.

microspheres of indomethacin are quite beneficial

for rheumatic patients.

Floating behaviour
The floating test on the microspheres is carried out
using the dissolution method II apparatus, specified
in the USP XXII. The microspheres are spread over
the surface of the dispersing medium (900 ml),
which is agitated by a paddle rotated at 100 rpm.
Disintegration test solution No. 1 (pH 1.2),
containing Tween 20 (0.02%, w/v), is used as a
dispersing medium to simulate gastric fluid. After
agitation for a previously determined interval, the
hollow microspheres that floated over the surface
of medium and those that settled to the bottom of
the flask are recovered separately. After drying,
each fraction of the hollow microspheres is
weighed. The buoyancy of the hollow microspheres
is represented by the following equation.

3. Floating microspheres are especially effective in

the delivery of sparingly soluble and insoluble
drugs. It is known that as the solubility of a drug
decreases, the time available for drug dissolution
becomes less adequate, and thus transit time
becomes a significant factor affecting drug
absorption.

where Qf and Qs are the weights of the floating and

settled hollow microspheres, respectively.

CONCLUSION:
Floating microspheres has emerged as an efficient
approach for enhancing the bioavailability and
controlled delivery of various therapeutic agents.
Significant attempts have been made worldwide to
explore these systems according to patient
requirements, both in terms of therapeutic efficacy
and compliance. Floating microspheres as gastro
retentive dosage forms precisely control the release
rate of target drug to a specific site and facilitate an
enormous impact on health care. Optimized multiunit floating microspheres are expected to provide
clinicians with a new choice of an economical, safe
and more bioavailable formulation in the effective
management of diverse diseases. These systems
also provide tremendous opportunities in the
designing of new controlled and delayed release
oral formulations, thus extending the frontier of
futuristic pharmaceutical development. Increased
sophistication of this system will ensure the
successful advancements in the avenue of gastro
retentive microspheres therapy so as to optimize
the delivery of molecules in a more efficient
manner.

In vitro release studies

In vitro dissolution studies can be carried out in a
USP
paddle
type
dissolution
assembly.
Microspheres equivalent to the drug dose are added
to 900 ml of the dissolution medium and stirred at
100 rpm at 37 0.5 C. Samples are withdrawn at a
specified time interval and analyzed by any suitable
analytical method, such as UV spectroscopy or
HPLC, etc.
In vivo studies
In vivo studies are generally conducted in healthy
male albino rabbits weighing 2-2.5 kg. The animals
are fasted for 24 hours before the experiments;
however, they are given free access to food and
water during the experiments. Blood samples (2
mL) are collected from the marginal ear vein into
heparinized centrifuge at an appropriate time
interval
Applications of floating microspheres
1. Floating microspheres can be used as carriers for
drugs with so-called absorption windows
for example antiviral, antifungal and antibiotic
agents (sulphonamides, quinolones, penicillins,
cephalosporins, aminoglycosides and tetracyclines)
are taken up only from very specific sites of the GI
mucosa.
2. Hollow microspheres of non-steroidal antiinflammatory drugs are very effective for
controlled release, and reduce the major side effect
of gastric irritation. For example, floating

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4. The gastroretentive floating microspheres will

beneficially alter the absorption profile of the
active agent, thus enhancing its bioavailability.
5. Hollow microspheres can greatly improve the
pharmacotherapy of the stomach through local drug
release, leading to high drug concentrations at the
gastric mucosa, thus eradicating Helicobacter
pylori from the sub-mucosal tissue of the stomach
and making it possible to treat stomach and
duodenal ulcers, gastritis and oesophagitis.

REFERENCES:
1. Praveen Nasa, Sheefali Mahant, Deepika
Sharma, Floating Systems: A Novel Approach
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D.M;
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Biopharmaceutics and Pharmacokinetics: A
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3. Chawla G; Gupta P; KoradiaV; And Bansal A.
K; Gastro retention: A Means to Address Regional

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Navya and A.Madhu Babu

Variability in Intestinal Drug Absorption

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